Medicines that act on the nervous system. Drugs acting on the central nervous system. Indications for use
List the signs of anesthesia.
The state of anesthesia is characterized by:
Analgesia – suppression of pain sensitivity;
Amnesia;
Loss of consciousness;
Suppression of sensory and autonomic reflexes;
Relaxation of skeletal muscles.
Name the main means for inhalation anesthesia.
1) Liquid volatile substances:
- halothane (fluorotane), enflurane, isoflurane, non-halogenated NS ( diethyl ether).
2) Gas drugs:
- nitrous oxide
Name the main means for non-inhalation anesthesia.
1) barbiturates: sodium thiopental.
2) non-barbituric NS: ketamine (calypsol), etomidate, propofol, propanidid, sodium oxybate.
Requirements for anesthesia.
· Smooth introduction to anesthesia without the stage of excitement.
· Sufficient depth of anesthesia to ensure optimal operating conditions.
· Good control over the depth of anesthesia.
· Quick recovery from anesthesia.
· Large therapeutic latitude - the range between the concentration at which a drug causes anesthesia and its minimum toxic concentration. Drugs are judged by their concentration in exhaled air, and non-inhalation drugs are judged by administered doses. The greater the narcotic breadth, the safer the drug.
· No side effects.
· Simplicity in technical application.
· Fire safety.
· Reasonable cost.
Name the stages of anesthesia.
1) Stage of analgesia.
2) Excitation stage.
3) Stage of surgical anesthesia:
Level 1 – superficial anesthesia.
Level 2 – light anesthesia.
Level 3 – deep anesthesia.
Level 4 ultra-deep anesthesia.
4) Stage of awakening (agonal - in case of overdose).
Functional characteristics of anesthesia.
1) Analgesia stage.
Characterized by suppression of pain sensitivity. Consciousness is preserved, but orientation is disturbed. Amnesia is typical.
2) Excitement stage.
Makes it difficult to induce anesthesia. Consciousness is lost, motor and speech excitation is observed, pupils are dilated, breathing becomes more frequent, tachycardia, arterial pressure fluctuates, cough, hypersecretion of bronchial and salivary glands, vomit. Possible cardiac arrest.
3) Stage of surgical anesthesia:
Consciousness is turned off, pain sensitivity is absent, reflex activity is suppressed, the pupils are constricted, blood pressure stabilizes, breathing becomes regular. As anesthesia deepens, the pulse rate changes, cardiac arrhythmias are possible, breathing is gradually depressed, skeletal muscles relax, jaundice may occur, renal function may be impaired
4) Awakening stage.
Analgesia persists for a long time, vomiting often occurs, but bronchopneumonia can develop.
What is minimum alveolar concentration (MAC). What properties of inhaled anesthetics can be judged by the value of this indicator?
During general anesthesia The partial pressure of the inhalational anesthetic in the brain is equal to that in the lungs when a steady state is achieved. Minimum alveolar concentration (MAC) is the concentration at which 50% of patients do not respond to the influence of a damaging factor (surgical incision). MAC is used to determine the effectiveness of the anesthetic.
The mechanism of the analgesic effect of anesthesia.
1) Interaction with the postsynaptic neuronal membrane, which causes a change in the permeability of ion channels, which disrupts the depolarization process and, consequently, the interneuronal transmission of impulses.
2) An increase in the intracellular concentration of calcium ions, a decrease in their uptake by mitochondria. This causes hyperpolarization of the membrane, increased permeability to potassium ions and, in general, a decrease in neuronal excitability.
3) Presynaptic action leading to a decrease in the release of excitatory mediators (ACh).
4) Interaction with the GABA-benzodiazepine-barbiturate receptor complex and potentiation of the action of GABA.
5) Inhibition of metabolic processes in CNS neurons.
Advantages of halothane anesthesia.
High narcotic activity.
Anesthesia occurs quickly with a short stage of excitation.
Anesthesia with fluorotane is easily manageable.
When inhalation is stopped, the patient wakes up within 5-10 minutes.
Anesthesia proceeds with quite satisfactory muscle relaxation. Ftorotan enhances the myoparalytic effect of anti-depolarizing curare-like drugs.
Does not cause irritation of mucous membranes, acidosis, nausea and vomiting in the post-anesthesia period.
Advantages of ether anesthesia.
Pronounced narcotic activity.
Sufficient narcotic breadth.
Relatively low toxicity.
Ether anesthesia is quite easy to manage.
Good muscle relaxation.
Advantages of anesthesia induced by nitrous oxide.
Does not cause side effects during surgery.
Does not have irritating properties.
It does not have a negative effect on parenchymal organs.
The rate of induction and recovery from anesthesia is very high.
Advantages of thiopental anesthesia.
Causes anesthesia in 1 minute without the stage of excitation.
The duration of anesthesia is 20-30 minutes.
Causes stronger muscle relaxation than hexenal.
Interaction between adrenaline and halothane.
When using fluorotane (halothane) possible cardiac arrhythmias. They are caused by the direct influence fluorotane on the myocardium, including its sensitization to adrenaline. In this regard, against the background of fluorotane anesthesia, the introduction adrenaline contraindicated.
Interaction between adrenaline and ethyl ether.
Interaction adrenaline And ethyl ether prevents possible reflex decrease in breathing and heart rate up to apnea and cardiac arrest.
Disadvantages of halothane anesthesia.
Bradycardia associated with increased vagal tone.
A decrease in blood pressure as a result of inhibition of the vasomotor center and sympathetic ganglia, as well as a direct myotropic effect on the vessels.
Cardiac arrhythmias are possible due to a direct effect on the myocardium, including its sensitization to adrenaline.
Ftorotan inhibits the secretory activity of the salivary, bronchial, and gastric glands.
In the body, a significant part of fluorotane (20%) undergoes biotransformation.
Disadvantages of ether anesthesia.
A pronounced stage of excitation, which is accompanied by tachycardia, fluctuations in blood pressure, cough, hypersecretion of the bronchial and salivary glands, and vomiting.
Low rate of induction and recovery from anesthesia.
Sometimes jaundice occurs.
Renal function is depressed and albuminuria is possible.
Acidosis develops.
Postoperative bronchopneumonia is possible.
Disadvantages of nitrous oxide anesthesia.
Low narcotic activity (there is no stage of deep anesthesia).
Does not cause muscle relaxation.
Nausea and vomiting are possible.
With long-term use, the development of leukopenia, megaloblastic anemia, and neuropathy is possible; this is due to the oxidation of cobalt in the cobalamin molecule.
Disadvantages of thiopental anesthesia.
Convulsive muscle twitching.
Laryngospasm.
Inhibitory effect on the respiratory and vasomotor centers, as well as the heart.
With rapid administration, apnea and collapse are possible.
Local irritant effect.
What is neuroleptanalgesia?
Neuroleptanalgesia is a special type of general anesthesia. It is achieved by the combined use of antipsychotics (neuroleptics), for example, droperidol, with an active narcotic analgesic (especially fentanyl). In this case, the antipsychotic effect is combined with pronounced analgesia. Consciousness is preserved. Both drugs act quickly and for a short time. This makes it easier to enter and exit neuroleptanalgesia.
What is combined anesthesia? Example.
Combined anesthesia is the combined administration of two or more anesthesia drugs. Combine inhalation anesthesia agents with inhalation or non-inhalation administered drugs. The positive thing is the rapid introduction of anesthesia and elimination of the stage of excitement. For example, anesthesia begins with the introduction thiopental-sodium, ensuring the rapid development of anesthesia without the stage of excitation. One of the most commonly used combinations of anesthesia is the following: a barbiturate or a strong drug for non-inhalational anesthesia + fluorotane + nitrous oxide. Advantage combined anesthesia It also lies in the fact that the concentration (dose) of the components in the mixture is less than when using one drug for anesthesia, therefore it is possible to reduce their toxicity and reduce the frequency of side effects.
What is potentiated anesthesia? Example.
Potentiated anesthesia is a combination of anesthetic agents with drugs of various effects, which is aimed at enhancing the narcotic effect. For example, midazolam. Its sedative and hypnotic effects are important.
What is induction anesthesia? Example.
Introductory anesthesia– intravenous administration of general anesthetics, ensuring rapid development of anesthesia without the stage of excitation. Sodium thiopental can be used.
Effect of ethanol on diuresis.
Diuretic effect ethyl alcohol has a central genesis (production of ADH by the posterior lobe of the pituitary gland decreases).
The effect of ethanol on the gastrointestinal tract.
Strengthens the secretory activity of the salivary and gastric glands. This is the result of a psychogenic, reflex, as well as direct effect on the glands. An increase in the secretion of gastric glands with direct exposure to alcohol on the mucous membrane is associated with the release of humoral substances (gastrin, histamine). It should be borne in mind that alcohol increases the secretion of hydrochloric acid. At low alcohol concentrations, pepsin activity does not change, but at high concentrations it decreases. When drinking strong drinks (40% or higher), stomach activity decreases. In response to irritation, the activity of goblet cells that secrete mucus increases. Gastric motility also changes: pyloric spasm and decreased motility. Alcohol has little effect on intestinal function.
The effect of ethanol on cardiovascular system.
Even when consumed in moderation ethanol inhibition of myocardial contractile function is noted. The cause of cardiac disorders is considered to be the accumulation of acetaldehyde, leading to changes in the reserves of catecholamines in the myocardium. Arrhythmias occur during alcohol withdrawal. Increases in blood pressure are associated with the amount of alcohol consumed, independent of obesity, salt intake, coffee consumption and smoking. dilatation of skin vessels and, as a result, increased heat transfer are also observed.
What is alcoholism?
Alcoholism is chronic poisoning with ethyl alcohol, which is characterized by various symptoms: decreased mental performance, attention, memory, may occur mental disorders, peripheral innervation and dysfunction of internal organs are also affected.
What is disulfiram?
White crystalline powder with a faint yellowish-greenish tint. Slightly soluble in alcohol, practically insoluble in water, acids and alkalis. Taken orally for the treatment of chronic alcoholism, in cases where it is not possible to obtain a therapeutic effect by other methods of treatment (psychotherapy, vitamin therapy, taking apomorphine and etc.).
The effect of the drug is based on its ability to specifically influence the metabolism of alcohol in the body. Alcohol undergoes oxidative transformations, passing through the acetaldehyde phase and acetic acid. With the participation of acetaldehydroxydase, acetaldehyde is usually rapidly oxidized.
Teturam, by blocking the enzymatic biotransformation of alcohol, leads to an increase in the concentration of acetaldehyde in the blood after drinking alcohol.
Side effects of Levopoda.
When using the drug, various side effects are possible: dyspeptic symptoms (nausea, vomiting, loss of appetite), orthostatic hypotension, arrhythmias, chronic and choreoathetoid hyperkinesis, headache, hyperhidrosis, etc. These phenomena decrease with lowering the dose. To avoid dyspeptic symptoms and for more uniform absorption, the drug is taken after meals.
What is codeine?
Synonym methylmorphine. An alkaloid found in opium; obtained semi-synthetically. Has pronounced antitussive activity.
What is methadone?
Opioid receptor agonist, diphenylpropylamine group.
What is trimepyridine?
Trimeperidine (promedol)) is a synthetic derivative of phenylpiperidine and, in its chemical structure, can be considered as an analogue of the phenyl-N-methylpiperidine part of the molecule morphine.
What is pentazacine?
Pentazocine- a synthetic compound containing the benzomorphane core of the morphine molecule, but lacking the oxygen bridge and the third six-membered core characteristic of compounds of the morphine group. It is an agonist of delta and kappa receptors and an antagonist of mu receptors.
What is buprenorphine?
Partial agonist of mu- and kappa receptors and antagonist of delta receptors.
What is tramadol?
Analgesic with a mixed (opioid and non-opioid) type of action.
What is naloxone?
Pharmacologically, naloxone differs in that it is a “pure” opiate antagonist, devoid of morphine-like activity. It acts as a competitive antagonism, blocking the binding of agonists or displacing them from opiate receptors. Naloxone has the greatest affinity for mu and kappa receptors. In large doses, the drug can give a slight agonistic effect, which, however, has no practical significance
What is dantrolene?
Centrally acting muscle relaxant. Used for the treatment of malignant hyperthermia, because inhibits the activation of catabolic processes.
What is nefopam?
Non-narcotic (non-opioid) analgesic.
What is baralgin?
Spasmoanalgesic.
What is sumatriptan?
Serotonin agonist (5HT 1 receptors)
What is ergotamine?
Ergot alkaloid is used to treat acute migraine attacks.
What is buspirone?
Non-benzodiazepine, atypical anxiolytic. Has a less pronounced sedative effect.
What is medazepam?
Benzodiazepine anxiolytic, long-acting daytime tranquilizer.
What is alprazolam?
A benzodiazepine anxiolytic, similar in structure to triazolam.
What is temazepam?
A benzodiazepine hypnotic with a pronounced hypnotic effect average duration actions.
What is oxazepam?
Medium-acting daily benzodiazepine tranquilizer.
What is chlordiazepoxide?
Long-acting benzodiazepine tranquilizer.
What is flumazenil?
Tranquilizer, benzodiazepine antagonist.
What is chlorpromazine?
APS, phenothiazine derivative, aliphatic agent.
What is chlorprothixene?
APS, a thioxanthene derivative.
What is haloperidol?
APS, butyrophenone derivative.
What is sulpiride?
Sulpiride is a sulfonylbenzamide derivative. By structure and some pharmacological properties sulpiride is also close to metoclopramide.
What is imipramine?
Imipramine is the main representative of typical tricyclic antidepressants. This is one of the first antidepressants, but due to its high effectiveness it is still widely used.
What is amitriptyline?
Amitriptyline, like imipramine, is one of the main representatives of tricyclic antidepressants. It differs in structure from imipramine in that the nitrogen atom in the central part of the tricyclic system is replaced by a carbon atom. It is an inhibitor of neuronal reuptake of transmitter monoamines, including norepinephrine, dopamine, serotonin, etc. It does not cause MAO inhibition.
What is sertraline?
Sertraline is an active selective inhibitor of neuronal serotonin reuptake; has little effect on recapture norepinephrine and dopamine.
What is moclobemide?
Moclobemide is an antidepressant - MAO inhibitor reversible action and also affects primarily MAO type A.
Main effects of bemitil.
It has a psychostimulating effect, has antihypoxic activity, increases the body's resistance to hypoxia and increases performance during physical activity. It is considered as a representative of a new group - actoprotective drugs. Slowly absorbed when taken orally. Prescribed to adults for asthenic conditions, neuroses, after injuries and other conditions in which stimulation of mental and physical functions is indicated. There is evidence of the immunostimulating effect of bemitil and its effectiveness in this regard in complex therapy some infectious diseases.
Effect of caffeine on the central nervous system.
Physiological features actions caffeine on the central nervous system were studied by I.P. Pavlov and his colleagues, who showed that caffeine enhances and regulates excitation processes in the cerebral cortex; in appropriate doses, it enhances positive conditioned reflexes and increases motor activity. The stimulating effect leads to increased mental and physical performance, reduced fatigue and drowsiness. Large doses can, however, lead to depletion of nerve cells. The effect of caffeine (as well as other psychostimulants) largely depends on the type of higher nervous activity; Dosing of caffeine should therefore be made taking into account the individual characteristics of nervous activity. Caffeine weakens the effect of sleeping pills and narcotics, increases reflex excitability spinal cord, excites the respiratory and vasomotor centers.
The effect of caffeine on the cardiovascular system.
Cardiac activity influenced caffeine intensifies, myocardial contractions become more intense and become more frequent. With collaptoid and states of shock blood pressure under the influence caffeine increases, with normal blood pressure no significant changes are observed, since simultaneously with the excitation of the vasomotor center and heart under the influence of caffeine, the blood vessels of skeletal muscles and other areas of the body (heart, kidneys) dilate, but the blood vessels of the organs abdominal cavity(except for the kidneys) narrow. The blood vessels of the brain narrow under the influence of caffeine, especially when they dilate.
The effect of caffeine on the gastrointestinal tract.
Influenced caffeine stimulation occurs secretory activity stomach. This can be used to differentiate between functional and organic gastric diseases.
Means affecting the central nervous system.
1. oppressive
2. exciting
Drugs that depress the central nervous system
Anesthetics
Anesthesia is a reversible state of the body in which pain sensitivity is turned off, consciousness is absent, reflexes are suppressed, while at the same time normal respiratory and cardiovascular function is maintained, i.e. artificially induced deep sleep with loss of consciousness and pain sensitivity. During anesthesia, favorable conditions are created for surgical operations.
Anesthetics have an inhibitory effect on the transmission of nerve impulses at synapses in the central nervous system. The sensitivity of synapses in different parts of the central nervous system to narcotic substances is not the same. Therefore, the inhibition of these departments under the influence of drugs does not occur simultaneously: first the more sensitive, then the less sensitive parts of the central nervous system are inhibited. Therefore, in the action of anesthesia, certain stages are distinguished, which replace each other as the concentration of the drug increases.
I stage– stunning (analgesia)(analgesia - loss of pain sensitivity (from Greek - an - denial, algos - pain).
When a narcotic substance enters the body, inhibition of the centers of the cerebral cortex first develops, which is accompanied by a decrease in pain sensitivity and a gradual depression of consciousness. By the end of the analgesia stage, pain sensitivity is completely lost, and at this stage some surgical procedures can be performed (opening abscesses, dressings, etc.) - Rausch anesthesia.
II stage–excitement
It manifests itself in the form of motor and speech excitation, unconscious attempts to get up from the operating table, disturbances in breathing rhythm, etc. Consciousness is completely lost, muscle tone sharply increases. Breathing and pulse are increased, blood pressure is increased. According to I.P. According to Pavlov, the cause of excitation at this stage is the switching off of the inhibitory influences of the cerebral cortex on the subcortical centers. A “subcortical riot” occurs.
III stage–surgical anesthesia
Characterized by suppression of the function of the cerebral cortex, subcortical centers and spinal cord. The phenomena of excitation pass, muscle tone decreases, reflexes are inhibited. Vital centers medulla oblongata– respiratory and vasomotor continue to function.
IV stage–awakening (recovery)
Occurs after cessation of drug administration. The functions of the central nervous system are restored.
Stage V –paralysis (agonal)
In case of an overdose of anesthetic, breathing becomes shallow, the activity of the intercostal muscles gradually fades, and breathing is impaired. Oxygen deficiency develops. Death can occur from paralysis of the respiratory and vasomotor centers.
Ethanol
It is a narcotic substance that has a depressant effect on the central nervous system. However, it cannot be used as an anesthetic, because has little narcotic breadth(the maximum possible range between the concentrations of a substance in the blood that causes surgical anesthesia and paralysis of vital important functions) and causes a long stage of excitement (intoxication). This stage is characterized by emotional arousal, increased mood, decreased critical attitude towards one’s own actions, disordered thinking and memory, decreased performance, etc.
With an increase in the dose of ethyl alcohol, the stage of excitation is replaced by depression of the central nervous system, coordination of movements and consciousness are impaired. Signs of depression of the respiratory and vasomotor centers appear.
Ethyl alcohol is easily absorbed from the gastrointestinal tract, mainly in small intestine and about 20% in the stomach. The resorptive effect manifests itself especially quickly when taken on an empty stomach. The absorption of alcohol is delayed by the presence in the gastrointestinal tract of such food products, like potatoes, meat, fats.
Alcohol has an effect on digestive system. Gastric secretion increases when exposed to alcohol in a concentration of no more than 20%. A further increase in alcohol concentration leads to a temporary decrease in secretion.
Under the influence of small doses of alcohol, first the superficial blood vessels dilate (the face turns red), and a feeling of warmth appears. With an increase in the concentration of alcohol in the blood, blood vessels dilate, especially in the abdominal cavity, and heat transfer increases. Therefore, persons in a state of alcohol intoxication, freeze faster than sober people.
IN medical practice The resorptive effect of ethyl alcohol is rarely used. It is sometimes used as an antishock agent (given its analgesic effect).
Practical use Ethyl alcohol is found due to its antimicrobial, astringent, and irritant properties. Antimicrobial action alcohol is due to its ability to cause denaturation (coagulation) of microorganism proteins and increases with increasing concentration. 95% ethyl alcohol is used for processing surgical instruments, catheters, etc. To clean the surgeon's hands and the surgical field, 70% alcohol is often used. This is due to the fact that alcohol of a higher concentration intensively coagulates the protein, but on the surface it does not penetrate the skin pores well.
The astringent effect of 95% alcohol is used to treat burns. Ethyl alcohol 40% concentration has pronounced irritating properties and is used to apply compresses for inflammatory diseases of internal organs, muscles, and joints.
Drinking alcohol can lead to acute poisoning, the degree of which depends on the concentration of alcohol in the blood. Intoxication occurs at 1-2 g/l, pronounced signs of poisoning appear at 3-4 g/l. In acute alcohol poisoning, a state of deep anesthesia develops, characterized by loss of consciousness, reflexes, sensitivity, and decreased muscle tone. Blood pressure drops, body temperature decreases, breathing becomes impaired, skin become pale. Death can occur from paralysis of the respiratory center.
First aid for acute poisoning with ethyl alcohol is to stop its further absorption into the blood. To do this, wash the stomach, give a saline laxative (20-30 g of magnesium sulfate per glass of water), if the patient is conscious, you can induce vomiting. For detoxification, a 40% glucose solution is administered intravenously, and a 4% sodium bicarbonate solution is administered intravenously to eliminate acidosis. If necessary, perform artificial respiration or administer oxygen and analeptics (bemegride, caffeine, etc.). It is necessary to warm the patient.
With chronic alcohol poisoning (alcoholism), performance sharply decreases, higher nervous activity, intelligence, attention, memory suffer, and mental illness often occurs. There are major changes in internal organs: chronic gastritis, cirrhosis of the liver, dystrophy of the heart, kidneys and other diseases.
Alcoholism is treated in hospitals. The main task is to stop drinking alcohol and develop aversion to it and negative reflexes to alcohol. One of the most effective drugs is Disulfiram(teturam). It delays the oxidation of ethyl alcohol at the level of acetaldehyde, the latter accumulates in the body and causes intoxication: headache, dizziness, palpitations, difficulty breathing, sweating, nausea, vomiting, and a feeling of fear. Long-acting disulfiram is produced for implantation under the skin - Esperal.
Sometimes emetics (apomorphine) are used to develop negative conditioned reflexes.
Treatment must be combined with psychotherapy.
Sleeping pills
Sleeping pills (hypnotics - from the Greek hypnos - sleep) - various substances chemical structure, which, under certain conditions, contribute to the onset and maintenance of sleep, normalize its parameters (depth, phase, duration).
Sleep is a vital need of the body. The mechanism of sleep is very complex. I.P. Pavlov made a great contribution to its study.
Sleep is not a homogeneous state and there are two phases in it, replacing each other several times (4-5). Sleep begins with the phase of “slow” sleep, which is characterized by a decrease in the bioelectrical activity of the brain, pulse, respiration, body temperature, gland secretion and metabolism. This phase accounts for 75-80% of the total sleep duration. It is replaced by the second phase - “rapid” sleep, during which the bioelectrical activity of the brain increases, pulse and breathing quicken, and metabolism increases. The REM sleep phase accounts for 20-25% of the total duration and is accompanied by dreams.
Insomnia (sleep disorders) may manifest itself as a delay in falling asleep or sleep patterns (short or interrupted sleep).
Sleep disorders are caused by various reasons:
Overwork;
Disturbance of the biological rhythm of life;
Pain, illness;
The stimulating effect of drinks, drugs, etc.
There are two types of insomnia:
- transient, which occurs when changing the usual lifestyle, emotional stress, workload, etc.
- chronic, which is an independent disease of the central nervous system.
For mild sleep disorders, hygienic measures are recommended: adherence to a routine, walks before bed, going to bed at the same time, using medicinal plants etc. The use of sleeping pills should be the last resort for correcting sleep. The duration of prescription of sleeping pills should not exceed three weeks
There are three groups of sleeping pills:
1 – derivatives of barbituric acid;
2 – benzodiazepines;
3 – products of different chemical structures.
The mechanism of action of sleeping pills lies in their ability to inhibit the transmission of impulses in various parts of the central nervous system. They stimulate inhibitory GABAergic processes in the brain through barbiturate (barbiturates) or benzodiazepine (benzodiazepine) receptors (Fig. 13). It is important to weaken the excitatory effect of the reticular formation on the cerebral cortex.
Barbituric acid derivatives
The sleep induced by barbiturates (as well as by most other sleeping pills) is different in structure from natural sleep. Barbiturates make it easier to fall asleep, but shorten the duration of REM sleep.
Phenobarbital(luminal) - long-acting drug: the hypnotic effect occurs after 1 hour and lasts 6-8 hours. It has a sedative, hypnotic, and anticonvulsant effect depending on the dose. Has cumulation. It is slowly neutralized in the liver, while stimulating the activity of microsomal enzymes, and is excreted mainly by the kidneys unchanged.
Cyclobarbital is part of a combination drug " Reladorm".
BDR – benzodiazepine receptor BRR – barbituric receptor
Fig. 13 Scheme of the GABA-benzodiazepine-barbiturate complex
with chlorine ionophore
Barbiturates are usually administered orally, less often rectally. After waking up, you may experience drowsiness, fatigue, and lack of coordination of movements.
Undesirable side effects manifest themselves in the occurrence of drug dependence with long-term use, respiratory depression, impaired renal and liver function, allergic reactions (rash), and low blood pressure.
Currently, they are rarely used as sleeping pills.
Acute poisoning barbiturates occur as a result of an accidental or intentional overdose of drugs. Central nervous system depression occurs, respiratory depression occurs, reflexes weaken, blood pressure drops; in case of severe poisoning, there is no consciousness (coma).
Treatment of acute poisoning consists of accelerating the elimination of drugs from the body and maintaining vital functions. If the drug is not completely absorbed from the gastrointestinal tract, gastric lavage is done, adsorbents and saline laxatives are given. Due to respiratory depression, oxygen therapy and artificial respiration are performed.
To speed up the elimination of already absorbed substances, diuretics are prescribed, and the method of forced diuresis is used. At high concentrations of barbiturates in the blood, peritoneal dialysis or hemodialysis is performed. Analeptics are used for mild forms of poisoning and are contraindicated for severe respiratory depression.
Benzodiazepine derivatives
They are safer drugs and have some advantages compared to barbiturates: they have less effect on the structure of sleep, however, with their long-term use, especially in large doses, daytime drowsiness, lethargy, fatigue, dizziness are possible, and the development of drug dependence is possible.
These drugs have a tranquilizing effect (see “ Psychotropic drugs"). The mechanism of the hypnotic effect (and other effects) of benzodiazepines is associated with an increase in the inhibitory effect of GABA (gamma-aminobutyric acid) in the central nervous system. GABA is the main inhibitory transmitter of the central nervous system, performing this function in all parts of the brain, including the thalamus, cortex, spinal cord, etc. From 30 to 50% of brain neurons are inhibitory GABAergic. Benzodiazepine derivatives, interacting with specific benzodiazepines receptors that are part of one of the subunits of the GABA receptor, increases the sensitivity of the latter to its mediator. When the GABA receptor is activated, a chloride channel opens; increased entry of chlorine ions into the cell causes an increase in membrane potential, while the activity of neurons in many parts of the brain decreases. (Fig.10)
Benzodiazepines shorten the period of falling asleep, reduce the number of night awakenings, and increase the total duration of sleep. They can be recommended both for difficulty falling asleep (especially associated with increased anxiety), but mainly for sleep disturbances in general and short sleep in older people.
Nitrazepam(radedorm, nitrosan) exhibits a strong hypnotic effect, affecting the subcortical structures of the brain, reduces emotional arousal and tension. Used for insomnia, as well as for neurosis of various origins. Sleep occurs within 20-45 minutes. after taking the medicine and lasts 6-8 hours.
Triazolam(halcion) has a pronounced hypnotic effect, speeds up falling asleep, and increases the total duration of sleep. Drug dependence is rare.
Flunitrazepam(rohypnol) has a sedative, hypnotic, anticonvulsant, and muscle relaxant effect. Used for sleep disorders, for premedication before anesthesia.
Contraindications to the use of benzodiazepines and other hypnotics are: pregnancy, lactation, liver and kidney dysfunction, alcoholism, central nervous system depression. It should not be administered to drivers, pilots and people in other professions that require quick reactions while working.
Listed benzodiazepines sleeping pills vary in duration of action, have different period half-life. T 0.5 of nitrazepam (and its active metabolites) is 24 hours, flunitrazepam - 20 hours, triazolam - up to 6 hours.
A specific antagonist of benzodiazepines is flumazenil. It blocks benzodiazepine receptors and eliminates completely or reduces the severity of most of the central effects of benzodiazepine anxiolytics. Flumazenil is usually used to eliminate the residual effects of benzodiazepines (for example, when used in surgery or in diagnostic procedures), as well as in case of overdose or acute poisoning.
The drug is usually administered intravenously. It acts for a short time - 30-60 minutes, so if necessary it is re-administered.
Sleeping pills of different chemical structures
Zopiclone(imovan, somnol, sonnatus), Zolpidem(ivadal, nitrest) are representatives of a new class of compounds, cyclopyrrolone derivatives, structurally different from benzodiazepines and barbiturates. The sedative-hypnotic effect of these drugs is due to the activation of GABAergic processes in the central nervous system. They quickly induce sleep without changing its structure, do not cause fatigue and drowsiness in the morning, do not accumulate and do not cause drug dependence. Used for treatment different types insomnia. They have a T of 0.5 for about 3-5 hours.
Undesirable effects: metallic taste in the mouth, nausea, vomiting, allergic reactions.
Bromized exhibits a predominantly sedative-hypnotic effect. To obtain a hypnotic effect, it is taken orally in powders and tablets, washed down with sweet warm tea or milk. There is no accumulation or addiction. Low toxic. In case of overdose and hypersensitivity to the drug, the phenomenon of “bromism” is possible: skin rash, conjunctivitis, dilated pupils, rhinitis.
Doxylamine(donormil) is an H1 blocker -histamine receptors. Reduces time to fall asleep. Has a cholinolytic effect. Causes dry mouth, constipation, and urinary problems. Other antihistamines also have a hypnotic effect (see “Antiallergic drugs”).
Analgesics
Analgesics (from the Greek – an – denial, algesis – sensation of pain) are called medicinal substances, which, with a resorptive effect, selectively suppress the feeling of pain. Pain is a symptom of many diseases and various injuries.
Pain sensations are perceived by special receptors called nociceptors(from Latin noceo - I damage). Irritants can be mechanical and chemical influences. Endogenous substances such as histamine, serotonin, bradykinin, etc., can cause painful sensations, affecting nociceptors. Currently, several types and subtypes of these receptors are known.
The body also has an antinociceptive (anti-pain) system. Its main elements are opioid peptides(enkephalins, endorphins). They interact with specific opioid(opiate) receptors involved in the conduction and perception of pain. Opioid peptides released in both the brain and spinal cord cause analgesia (pain relief). An increased release of endogenous analgesic peptides is observed when severe pain occurs.
Analgesics, unlike anesthetics, selectively suppress only pain sensitivity and do not impair consciousness.
Pyrazolone derivatives
Metamizole sodium(analgin) has an anti-inflammatory, antipyretic effect, but the analgesic effect is more pronounced. It is highly soluble in water, so it is often used for parenteral administration. Included in combination drugs " Tempalgin», « Pentalgin», « Benalgin", as well as in combination with antispasmodics in the composition of drugs " Baralgin», « Spazgan», « Maxigan", effective for spasmodic pain.
Undesirable side effects: inhibition of hematopoiesis (agranulocytosis), allergic reactions, gastrotoxicity. During treatment, monitoring of blood tests is necessary.
Aniline derivatives
Acetaminophen(paracetamol, Panadol) has an analgesic and antipyretic effect and has almost no anti-inflammatory effect. It is used mainly for headaches, neuralgia, injuries, and fever. Widely used in pediatrics in the form of syrups and effervescent tablets– Eh Ferralgan, Tylenol, Calpol, Solpadeine, Paracet and others. Drugs practically do not cause irritation of the gastric mucosa. Possible dysfunction of the liver and kidneys. The antagonist of paracetamol is acetylcysteine.
Non-narcotic analgesics are contraindicated in peptic ulcer stomach and duodenum, impaired liver and kidney function, bronchospasms, hematopoietic disorders, pregnancy, lactation.
Chapter 3.3 Medicines affecting the central nervous system
The central nervous system is of paramount importance for the functioning of the body. Disruption of its normal functioning can lead to serious illnesses.
All medicinal substances acting on the central nervous system can be divided into two groups:
1. oppressive functions of the central nervous system (anesthetics, hypnotics, anticonvulsants, narcotic analgesics, some psychotropic drugs (neuroleptics, tranquilizers, sedatives);
2. exciting functions of the central nervous system (analeptics, psychostimulants, general tonics, nootropics).
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
THE CARDIOVASCULAR SYSTEM
A moderate amount of ethanol causes dilation of skin vessels (a central effect, since depression of the central nervous system leads to inhibition of the vasomotor center), which is accompanied by hyperemia and a feeling of warmth. A person who has taken ethanol has a red face and his eyes “burn.” The effect of vasodilation under the influence of ethyl alcohol prevents the normal reaction of constriction of skin vessels during cooling, therefore 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 may develop alcoholic hepatitis, cirrhosis of the liver. Alcohol liver damage is a direct effect of ethanol. Women are more sensitive to the effects of alcohol, which is associated with a genetic predisposition based on the HLA phenotype.
Alcohol increases urination, which is a consequence of reduced reabsorption of water in the renal tubules, caused by inhibition of ADH (antidiuretic hormone) production.
EFFECT ON THE GASTROINTESTINAL TRACT
In small doses, when taken orally, ethanol causes a local sensation of warmth and increases the secretion of saliva and increases appetite. Due to the release of histamine and gastrin in the antrum, the secretion of the gastric glands increases.
At a concentration of more than 15 percent, alcohol inhibits both secretion and motor function. This effect can last for many hours. Even higher concentrations have a pronounced irritating effect on the mucous membranes and can cause the development of gastritis, provoke nausea and vomiting. At concentrations of more than 20 percent, the enzymatic activity of both gastric and intestinal juice decreases. When drinking alcohol in a concentration of over 40 percent, there is a burn of the mucous membrane, its swelling, swelling, destruction of the boundary layer of the mucous membrane, and the release of mucus in large quantities.
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 was previously used to destroy nerve fibers, for example, in neurology trigeminal nerve. Now this method is practically not used.
7) To prevent bedsores, lubricating the patient’s skin.
Due to wide range effects 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 (washing), maintaining vital function important organs(breathing, heart), reducing cerebral edema with mannitol and intravenous administration glucose to correct hypoglycemia, alkalization using intravenous administration of 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 highest degree substance toxic 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 turns 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 lesions, atherosclerosis, angina pectoris, hypertonic disease, 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, anesthetics such as paraldehyde should not be used, as they cause effects similar to those of ethanol. In addition, some medications 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 sulfa 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 implanted into subcutaneous tissue patient (creation of 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 specifically, selectively acts on 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.
The dream is a vital necessity for a person. Healthy people spend approximately 1/3 of their lives sleeping. At the same time, it is extremely important factor A person's health is to get enough sleep. 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 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, varies from person to person. different persons. 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(excitement, 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, the patient is sometimes helped simple procedures: patients should not sleep during the day; a few hours before bedtime they should be advised to take a small 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 general recommendations 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 the one noted above, is that barbiturates significantly disrupt the normal structure of sleep.
In the structure of sleep healthy person There are 2 types of sleep. This division was made 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, eyeballs are in rapid motion, 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) Develops towards barbiturates drug addiction(mental and physical).
In addition, to side effects also include agitation, headache, vomiting, muscle pain, allergic reactions, 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. Central nervous system 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, the 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 found wide application as a sleeping pill. 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, worry, 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 resulting 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 anesthetics, 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.
Central nervous system, its structure and functions. Control of body functions, ensuring its interaction with environment. Neurons and their role in receiving and transmitting information, maintaining the vital functions of our body. Diseases of the central nervous system as disturbances in the processes of receiving and transmitting information within it. Medicines used in treatment various diseases central nervous system.
The nervous system coordinates the activities of the cells, tissues and organs of our body. It regulates the functions of the body and its interaction with the environment, provides opportunities for the implementation of mental processes that underlie the mechanisms of perception and thinking, memorization and learning.
The nervous system is a complex complex of highly specialized cells that transmit impulses from one part of the body to another, as a result the body is able to respond as a whole to changes in external or internal environmental factors.
Anatomically, the central and peripheral nervous systems are distinguished.
The central nervous system is represented by the brain and spinal cord.
The brain, consisting of the cortex with its numerous convolutions and the subcortex, is located in the cranial cavity. Brain mass in adults ranges on average from 1100 to 2000. From 20 to 60 years of age, brain mass and volume remain constant for each individual. If you straighten the convolutions of the cortex, it will occupy an area of approximately 20 m2.
The spinal cord is an oblong, cylindrical cord located in the spinal column. Its upper border is located at the base of the skull, and its lower border is located at the I-II lumbar vertebrae. The upper parts of the spinal cord pass into the brain, the lower parts end with the conus medullaris. The length of the spinal cord in an adult is on average 50 cm, the diameter is about 1 cm and the weight is about 34-38 g.
The peripheral nervous system includes nerve fibers and nodes located outside the central nervous system.
The main structural and functional element of the nervous system are nerve cells - neurons . A collection of neurons and their surroundings cellular elements forms nerve tissue, the structure of which you became acquainted with in.
Neurons are distinguished from other types of specialized cells by the presence of several processes that ensure the conduction of nerve impulses throughout the human body. One of the shoots - axon , as a rule, longer than the others. Axons can reach a length of 1-1.5 m. These are, for example, the axons that form the nerves of the limbs. However, they are only part of a single cell. The axons end in several thin branches - nerve endings. These endings functional significance can be sensitive, executive and providing interneuron contacts.
Nerve cells differ in structure, but all their types are united by a main feature: the ability to perceive irritation, enter a state of excitation, produce an impulse and transmit it further. Some neurons respond to influences from the external or internal environment and transmit impulses to the central parts of the nervous system. Such neurons are called sensitive. They, like sensors, permeate our entire body. They constantly measure temperature, pressure, composition and concentration of environmental components and other indicators. If these indicators differ from the standard ones, sensitive neurons send impulses to the corresponding part of the nervous system. The nervous system responds to these impulses and sends signals through executive neurons to tissues and organs, prompting them to act. This action becomes a corresponding decrease or increase in the production of biologically active substances by cells ( secret ), expansion or contraction blood vessels, contraction or relaxation of muscles.
The nervous system provides reflexive, unconscious reactions of the body to environmental influences. In we gave a description of the simplest reflex arc (see), in which there is a direct connection between sensitive and executive neurons. Such a connection underlies any reflex reaction that occurs without the participation of consciousness. Indeed, we have no time to think when we touch a hot stove. If we start thinking: “My finger is on a hot stove, it’s burned, it hurts, I should remove my finger from the stove,” then the burn will occur much earlier than we take any action. We simply pull our hand away without thinking and without having time to realize what happened. This is an unconditioned reflex and for such a response, the connection of the sensory and executive nerves at the level of the spinal cord is sufficient. We encounter similar situations thousands of times and simply don’t think about it.
Other reflex responses are very complex and involve many sensory and executive neurons.
Reflexes that are carried out with the participation of the brain and are formed on the basis of our experience are called conditioned reflexes. We act according to the principle of a conditioned reflex when we drive a car or perform various mechanical movements. Conditioned reflexes make up a significant part of our daily activities.
Regardless of the type of neurons, the transmission of a nerve impulse along their chain occurs chemically in places of convergence nerve endings one neuron to others. These interaction points are called synapses (Look ). The presynaptic part of the interneuron contact contains vesicles with a mediator ( mediator ), which release this chemical agent in synaptic cleft when a pulse passes. Next, the transmitter interacts with specific receptors on the postsynaptic membrane, as a result of which the next nerve cell enters a state of excitation, which is transmitted even further along the chain. This is how nerve impulses are transmitted in the nervous system. You can learn more about the operation of the synapse in the next chapter. The role of mediator is performed by various biological active substances: acetylcholine , norepinephrine , dopamine , glycine , gamma-aminobutyric acid (GABA) , glutamate , serotonin and others. Mediators of the central nervous system are also called neurotransmitters .
What we call a nerve is a collection of nerve fibers surrounded on the outside by a common connective tissue sheath. Each fiber, in turn, is composed of many sensory and motor nerve processes, also surrounded by a single connective tissue sheath. Nerves conduct impulses along a chain of neurons and from them to cells of other tissues. The cell bodies of neurons themselves can be located in the central nervous system or in peripheral nodes.
Drugs affecting the central nervous system were apparently discovered as early as primitive people. They are used both for medicinal purposes and to maintain vitality or create a subjective feeling of inner comfort. Everyone knows the effects of caffeine, alcohol and nicotine. Often we have to resort to painkillers, sleeping pills. Everyone knows about the properties of narcotic substances - opium, hashish, cocaine, marijuana and others. All these substances act mainly on the central nervous system, or through it and with its help on other organs.
However, excessive or prolonged consumption of substances that affect the functions of the central nervous system leads to the development of addiction, mental and physical dependence of a person on such drugs. And what was useful and helped yesterday becomes poison that destroys our body. A person can no longer do without another, each time more and more high dose(this especially applies to narcotic drugs and alcohol). But after temporary relief, a difficult period begins again, so difficult that in order to receive a new dose, a person ceases to control his actions and coordinate them with moral standards, he degrades. Damage is gradually caused to other organs and systems ( cardiovascular system, digestive system and so on). The person becomes disabled and dies. A drug addict is no longer able to change his life on his own; only the help of doctors can save him from inevitable death.
From large quantity Substances that depress the central nervous system are used: narcotic, hypnotic, neuroleptic, tranquilizing, sedative, analgesic and antipyretic.
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).
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 (6, p. 45).
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.
1. Anesthesia.
2. Ethyl alcohol.
3. Sleeping pills.
4. Antiepileptic drugs.
5. Antiparkinsonian drugs.
6. Analgesics.
7. Analeptics.
8. Psychotropic drugs:
neuroleptics;
tranquilizers;
sedatives;
lithium salts;
antidepressants;
psychostimulants;
g) nootropic drugs.
Among the listed substances there are medicines, which 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.
In contrast to these substances, some drugs act on the central nervous system in a stimulating manner (for example, analeptics, psychostimulants).
There are also substances that can have a depressing effect on some nerve centers and a stimulating effect on others. For example, narcotic analgesics inhibit the perception of pain, the respiratory center, and the cough center, but stimulate the vagus and oculomotor centers.
I would like to give another classification of drugs that affect the central nervous system
Drugs of the strychnine group (medicines that primarily stimulate the functions of the spinal cord)
Treatments mental illness and neuroses (psychotropic drugs)
Anesthetics
Means for non-inhalation anesthesia
Central nervous system stimulants, analeptic drugs
Drugs that have a “tonic” effect on the central nervous system
Drugs used to treat parkinsonism
Products that improve intellectual activity of the brain/attention, memory, learning, etc. / nootropic and gamkergic drugs)
Tricyclic antidepressants
Points of action of drugs affecting the central nervous system
1 - impulse in the presynaptic fiber;
2 - synthesis of mediator;
3 - mediator storage;
4 - metabolism in the presynaptic terminal (metabolism);
5 - release of the mediator;
6 - recapture of the mediator;
7 - destruction of the mediator (degradation);
8 - receptor;
9 - increase or decrease in ionic conductivity
Conclusion
Thus, substances affecting the autonomic nervous system can be classified as follows:
Adrenergic agents
Antiadrenergic agents
Cholinergics
Anticholinergic drugs
However, excessive or prolonged use of substances that affect the functions of the central nervous system leads to the development of addiction, mental and physical dependence of a person on such drugs. And what was useful and helped yesterday becomes poison that destroys our body. A person can no longer do without another, each time higher dose (this especially applies to drugs and alcohol). But after temporary relief, a difficult period begins again, so difficult that in order to receive a new dose, a person ceases to control his actions and coordinate them with moral standards, he degrades. Damage is gradually caused to other organs and systems (cardiovascular system, digestive system, and so on). The person becomes disabled and dies. A drug addict is no longer able to change his life on his own; only the help of doctors can save him from inevitable death.
Bibliography
1. Vein A.M., Solovyova A.D. and Kolosova O.A. Vegetovascular dystonia, M., 1981;
2. Gusev E.I., Grechko V.E. and Burd G.S. Nervous diseases, p. 199, 547, M., 1988;
3. Lobko P.I. and others. Autonomic nervous system. Atlas, Minsk, 1988;
4. Nozdrachev A.D. Physiology of the autonomic nervous system, L., 1983, bibliogr.;
5. Pathological and anatomical diagnosis of human tumors, ed. ON THE. Kraevsky et al., p.86, M., 1982;
6. Paches A.I. Tumors of the head and neck, p. 90, M., 1983;
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