For more than a hundred years, drugs such as barbiturates have been known in medicine. The list of these substances has been greatly reduced in lately, because it turned out that they can cause severe addiction and severe side effects. But, despite this, such drugs are still used in medicine, although they cannot be found on the open market. This is explained by the fact that in the middle of the 20th century there were a lot of deaths due to barbiturate poisoning. Therefore, those to whom a doctor prescribes these drugs for treatment need to know what side effects they can cause. In addition, there are modern, more effective and safe medications.
These medicines appeared at the very beginning of the 20th century. The German scientist Bayer discovered a special substance - barbituric acid. Already in 1903, the first medicine “Barbital” was released for sale, more often found under the name “Veronal”.
By the middle of the century, more than two thousand drugs were known, which were called “barbiturates”. Their use in medicine was wide: from simple insomnia to anesthesia. Many took these drugs for stress, sleep problems, or simply to calm down. Some became dependent on barbiturates, which was often fatal. Therefore, in the 70s, these drugs disappeared from free sale. And now some barbiturates are used only in rare cases.
Nowadays there are hardly more than a dozen such drugs left in use. There are several groups of barbiturates. They were divided by duration of action. The following barbiturates can be distinguished:
Long-acting: “Barbital”, “Phenobarbital” (better known as “Luminal”), “Sodium Barbiturate”, “Butizol” and others;
Medium duration: “Cyclobarbital”, “Barbamil”, “Alurat”, “Butabarbital”, “Talbutal” and others;
With a short (up to 6 hours) effect: Hexobarbital, Pentotal, Thiamylal, Brevital and other drugs. They are usually used as intravenous injections, within a few minutes after administration.
Barbituric acid began to be used in medicine, as it turned out that it affects the human central nervous system: it blocks contacts between nerve cells. Therefore, all these drugs have a strong sedative, anticonvulsant, slight analgesic and hypnotic effect. If you take barbiturates before anesthesia, they will enhance its effect.
Now they are equated to drugs, since use not only depresses the nervous system, but is also highly addictive. The effect of barbiturates can be compared to alcohol. They cause the same state of euphoria and excitement, often aggression, then a deep, heavy sleep, after which the person feels depressed and wants to take the drug again. People who use barbiturate drugs report feeling relaxed and calm, with increased self-confidence and sociability. It is because of these effects that many become dependent on drugs. You can find out by testing: barbiturates are detected in the urine. The reasons for this are that barbituric acid is excreted mainly through the kidneys.
It has long been proven that these drugs cause severe illness, often resulting in death. But in some cases, only barbiturates can help the patient. The list of drugs currently used in medicine has been greatly reduced, but they can only be purchased with a doctor’s prescription.
They are prescribed only in extreme cases:
Under severe stress;
Serious nervous disorders;
For seizures and convulsions;
To prepare the patient for anesthesia during operations;
In case of insomnia, when other remedies do not help.
Barbiturates are mainly used for epilepsy. But some older, lonely people also use them to calm themselves down. In medical institutions, barbiturates are used in the form of intravenous or intramuscular injections, and for outpatient treatment Tablets, capsules or suppositories may be prescribed. Some drugs are found in other medications. For example, phenobarbital is the basis of Corvalol. And the strong sleeping pill Penobarbital is used for executions or euthanasia in veterinary medicine.
Nowadays, barbiturates are mainly used in medical institutions. The list of drugs approved for use is known only to specialists. It is very easy to get poisoned by such drugs or become dependent on them. If a person frequently uses barbiturates, this can be recognized by the following signs:
Drowsiness, confusion, frequent hallucinations;
Poor balance and uncontrolled movements;
Slurred speech, stuttering;
Decreased immunity;
Rash and purulent diseases skin;
And slowing down the action of the gastrointestinal system;
Depression, absent-mindedness, but sometimes aggressiveness;
Retardation of consciousness and impaired concentration.
People who often use such drugs to calm down or combat insomnia sometimes do not even suspect the danger they pose. After all, barbiturates are now considered drugs along with opium. Dependence manifests itself in the need to constantly take drugs, increasing their dose.
It develops after three months of regular use. Addiction leads to irritability, absent-mindedness, decreased concentration and memory. Various neurological disorders: tremors of limbs, convulsions. After a heavy sleep caused by barbiturates, a person feels completely exhausted. His blood pressure is low and he is experiencing severe headache and nausea, to get rid of it, he takes a new dose of the drug. This is how he becomes dependent.
Since their inception, barbiturates have become very popular. By the middle of the 20th century, the list of drugs had grown to two and a half thousand names. They were taken by those who needed to calm down and get rid of problems, who experienced constant tension and problems falling asleep. After it was discovered that the effects of barbiturates were similar to narcotics, their use was greatly reduced. But even now many become dependent on them. It is believed that these are most often themselves, having lost interest in life and the need for communication. And despite the fact that barbiturates cause oblivion, heavy sleep and lack of thoughts, they remain popular. This is often why people tend to take such drugs. And besides, under their influence a person stops feeling pain, experiencing emotions and relaxes.
The danger of using these drugs is that an overdose of the drug can quickly occur. This leads to the fact that a person falls asleep and may not wake up, as breathing gradually slows down and death occurs. If barbiturates are in the blood in large quantities, and this can occur even when taking a regular dose, but in the case of prolonged use of the drug, poisoning occurs. A person’s blood pressure drops sharply, his face turns blue, and his breathing becomes frequent and shallow. Death usually occurs from paralysis of the respiratory system.
It is very difficult to get rid of barbiturate addiction.
The withdrawal syndrome is often stronger than with opium addiction. Within a couple of days after stopping taking the drugs, a person feels anxiety, nausea, suffers from insomnia and convulsions. Epileptic seizures, bronchospasm, or coma may occur. This often leads to death. Psychological disorders are also observed: a person cannot think clearly, suicidal tendencies arise. Therefore, such dependence can only be treated in medical institution under the supervision of a doctor.
Recently, such drugs are used less and less. In many countries, barbiturates are generally prohibited. Not everyone knows what medications they are used in, so you need to carefully read the ingredients in the instructions. And to get rid of insomnia and stress, more safe drugs, which very rarely cause addiction. Most often these are Lorazepam, Diazepam, Librium and others. Even safer are “Novo Passit”, “Glycine”, “Zelenin Drops” and others homeopathic medicines. An alternative to chemical remedies may be herbal infusions of mint or motherwort, aromatherapy, acupuncture, or lifestyle changes.
Dependence on drugs included in the group of barbiturates is considered narcotic. The need for taking these drugs is also great, as with other types of drug addiction. Those who are not familiar with medicine will definitely have a question: birbiturates - what is it? Why are they dangerous and why are they addictive? Let's try to answer this question in an understandable form.
Barbiturates are drugs made from barbituric acid. The drugs have a calming and mild hypnotic effect, which is caused by depression of the central nervous system. The insidious drug barbiturate as part of various sedatives is taken by many people who experience anxiety, fear, or suffer from insomnia. A one-time dose of the drug is justified in case of extremely severe overexcitation or frustration, but in no case should you take the medicine regularly.
IN recent years in medical practice, they began to abandon the widespread use of these drugs, since statistics indicate that ordinary people who are not at all trying to achieve a narcotic effect have begun to suffer from dependence on popular drugs. Therefore, barbiturate drugs are now prescribed with great caution, and in some countries they are prohibited.
To say about barbiturates that it is exclusively harmful substances, is not entirely true, since one-time doses do not lead to pathological changes in the body. But patients rarely comply with doctor’s orders, taking medications “at their own discretion.” Hence there are many sad consequences, including the emergence of new types of drug addiction, one of which is “barbiturate mania.”
Modern medicine is switching to more harmless drugs, retaining the use of barbiturates in the treatment of such serious illnesses like epilepsy, as well as some other mental illnesses.
So, we have already found out what a barbiturate is and when it is used. Now it’s worth clearly articulating what symptoms indicate the development of dependence on the drug. Under the influence of barbiturates, a person becomes sleepy, experiencing indifference to stress factors. Slows down physical activity and mental activity. When the effect of the drug ends, nervousness, irritability, absent-mindedness, and changes in reflexes appear.
With regular and long-term use of medications, severe withdrawal syndrome. As a rule, a deterioration in well-being occurs when the drug is abruptly discontinued: a person experiences restlessness, anxiety, gets tired quickly, gets cold (barbiturates constrict blood vessels), and sleeps poorly. In the most severe cases, abdominal pain, vomiting and nausea occur. The patient loses weight, loses appetite and interest in life. On the fifth day after stopping the medication, convulsions may occur (without loss of consciousness).
Only a narcologist can answer the question of how to cure addiction to barbiturates. Many factors are taken into account when prescribing a therapeutic program: the degree of poisoning of the body, age, the presence of concomitant diseases and other important points. Treatment is designed for a long period, as with other types of drug addiction.
Barbiturates are derivatives of barbituric acid. Since their creation and introduction into practice in 1903, they have become widespread throughout the world as hypnotics and anticonvulsants. In the practice of anesthesiology, they have been used longer than all other intravenous anesthetics.
In recent years, they have given way to the dominance of hypnotics that they held for several decades. Currently, the list of barbiturates used for anesthesia is limited to sodium thiopental, methohexital and hexobarbital. Sodium thiopental was the standard hypnotic for inducing anesthesia from 1934 until the introduction of propofol in 1989. Phenobarbital (see section III), which is administered orally, can be used as a premedication.
The classification of barbiturates by duration of action is not entirely correct, since even after the use of ultra-short-acting drugs, its residual plasma concentration and effects last for several hours. In addition, the duration of action changes significantly with the infusion route of administration. Therefore, the division of barbiturates is justified only by the nature of the chemical substitution of carbon atoms in barbituric acid. Oxybarbiturates (hexobarbital, methohexital, phenobarbital, pentobarbital, secobarbital) retain the oxygen atom in the position of the 2nd carbon atom. In thiobarbiturates (sodium thiopental, thiamylal), this atom is replaced by a sulfur atom.
The effect and activity of barbiturates depend largely on their structure. For example, the degree of chain branching at the 2nd and 5th carbon positions in the barbiturate ring determines the strength and duration of the hypnotic effect. This is why thiamylal and secobarbital are stronger than sodium thiopental and last longer. Replacing the 2nd carbon atom with a sulfur atom (sulfurization) increases fat solubility, which means barbiturates are a powerful hypnotic with a rapid onset and shorter duration of action (sodium thiopental). The methyl group at the nitrogen atom determines the short duration of action of the drug (methohexital), but causes a greater likelihood of excitation reactions. The presence of a phenyl group at the position of the 5th atom imparts increased anticonvulsant activity (phenobarbital).
Most barbiturates have stereoisomers due to rotation around the 5th carbon atom. With the same ability to penetrate the central nervous system and similar pharmacokinetics, the 1-isomers of sodium thiopental, thiamylal, pentobarbital and secobarbital are almost 2 times stronger than the d-isomers. Methohexital has 4 stereoisomers. The beta-1 isomer is 4-5 times stronger than the a-1 isomer. But the beta isomer determines excessive physical activity. Therefore, all barbiturates are available as racemic mixtures.
Currently, barbiturates are used mainly for the induction of anesthesia. Typically, hexobarbital and methohexital are administered as a 1% solution, and sodium thiopental as a 1-2.5% solution. Loss of consciousness based on clinical and EEG signs does not reflect the depth of anesthesia and may be accompanied by hyperreflexia. Therefore, traumatic manipulations, including tracheal intubation, should be performed with the additional use of other drugs (opioids). The advantage of methohexital is more fast recovery consciousness after its administration, which is important for outpatient conditions. But it is more likely than sodium thiopental to cause myoclonus, hiccups and other signs of agitation.
Barbiturates are now rarely used as a component of maintaining anesthesia. This is determined by the presence of side effects and inappropriate pharmacokinetics. They can be used as a monoanesthetic for cardioversion and electroconvulsive therapy. With the advent of BD, the use of barbiturates as premedications was sharply limited.
In the intensive care unit and intensive care(ICU) barbiturates are used to prevent and relieve seizures, to reduce ICP in neurosurgical patients, and less commonly as sedatives. The use of barbiturates to achieve sedation is not justified in the setting of pain. In some cases, barbiturates are used to relieve psychomotor agitation.
In animal experiments, it was found that high doses of barbiturates lead to a decrease in mean blood pressure, MK and PM02 Methohexital has less of an effect on metabolism and vasoconstriction than sodium thiopental, and also acts more briefly. By creating cerebral artery occlusion, barbiturates reduce the infarct area but have no benefit in stroke or cardiac arrest.
In humans, sodium thiopental at a dose of 30-40 mg/kg body weight provided protection during heart valve surgery under normothermic cardiopulmonary bypass (CPB). Thiopental sodium protects poorly perfused areas of the brain in patients with increased ICP against the background of carotid endarterectomy and aneurysm thoracic aorta. But such high doses of barbiturates cause severe systemic hypotension, require greater inotropic support and are accompanied by a long period of awakening.
The ability of barbiturates to improve brain survival after general ischemia and hypoxia due to traumatic brain injury or circulatory arrest has not been confirmed.
The mechanism of CNS depression by drugs for IV anesthesia is not completely clear. By modern ideas There is no universal mechanism for all general anesthetics. The lipid and protein theories were replaced by the theory of ion channels and neurotransmitters. As is known, the functioning of the central nervous system occurs under conditions of a balance of systems that activate and inhibit the conduction nerve impulses. GABA is considered the main inhibitory neurotransmitter in the central nervous system of mammals. Its main site of action is the GABA receptor, which is a hetero-oligomeric glycoprotein complex consisting of at least 5 regions united around the so-called chloride channels. Activation of the GABA receptor leads to an increased flow of chlorine ions into the cell, hyperpolarization of the membrane and a decrease in the response of the postsynaptic neuron to excitatory neurotransmitters. In addition to the GABA receptor, the complex contains benzodiazepine, barbiturate, steroid, picrotoxin and other binding sites. IV anesthetics may interact differently with different parts of the GABAA receptor complex.
Barbiturates firstly reduce the rate of dissociation of GABA from the activated receptor, thereby prolonging the opening of the ion channel. Secondly, in somewhat higher concentrations, they, imitating GABA even in its absence, directly activate chloride channels. Unlike BD, barbiturates are not so selective in their action; they can suppress the activity of excitatory neurotransmitters, incl. outside the synapses. This may explain their ability to induce surgical anesthesia. They selectively inhibit the conduction of impulses in the ganglia of the sympathetic nervous system, which, for example, is accompanied by a decrease in blood pressure.
Barbiturates have a dose-dependent sedative, hypnotic, and anticonvulsant effect.
Depending on the dosage, barbiturates cause sedation, sleep, and in cases of overdose, surgical anesthesia and coma. The severity of sedative-hypnotic and anticonvulsant effects of different barbiturates is not the same. According to the relative potency of the effect on the central nervous system and the vagus nerve system, they are arranged in the following order: methohexital > thiamylal > sodium thiopental > hexobarbital. Moreover, in equivalent doses, methohexital is approximately 2.5 times stronger than sodium thiopental and its effect is 2 times shorter. The effect of other barbiturates is less strong.
In subanesthetic doses, barbiturates can cause increased sensitivity to pain - hyperalgesia, which is accompanied by lacrimation, tachypnea, tachycardia, hypertension, and agitation. On this basis, barbiturates were even considered anti-analgesics, which was not subsequently confirmed.
The anticonvulsant properties of barbiturates are due mainly to postsynaptic activation of GABA, changes in membrane conductance for chloride ions, and antagonism of glutaminergic and cholinergic excitations. In addition, it is possible to presynaptically block the entry of calcium ions into nerve endings and decreased transmitter release. Barbiturates have varying effects on seizure activity. Thus, sodium thiopental and phenobarbital can quickly stop seizures when other drugs are ineffective. Methohexital may cause seizures when used in high doses and prolonged infusion.
Electroencephalographic changes caused by barbiturates depend on their dose and differ in phase: from low-voltage fast activity after the administration of small doses, mixed, high-amplitude and low-frequency 5- and 9-waves with deepening anesthesia to bursts of suppression and flat EEG. The picture after loss of consciousness is similar physiological sleep. But even with such an EEG picture, intense painful stimulation can cause awakening.
The effect of barbiturates on evoked potentials has its own peculiarities. A dose-dependent change in somatosensory evoked potentials (SSEPs) and auditory evoked potentials (AEPs) of the brain is observed. But even when isoelectric EEG is achieved during the administration of sodium thiopental, SSEP components are available for recording. Thiopental sodium reduces the amplitude of motor evoked potentials (MEPs) to a greater extent than methohexital. The Bispectral Index (BIS) is a good measure of the hypnotic effect of barbiturates.
Barbiturates are considered drugs that provide brain protection. In particular, phenobarbital and sodium thiopental suppress electrophysiological, biochemical and morphological changes resulting from ischemia, improving the recovery of pyramidal cells of the brain. This protection may be due to a number of direct neuroprotective and indirect effects:
However, it should be remembered that high doses of barbiturates, along with their negative hemodynamic effect, increase immunosuppression, which may limit their clinical effectiveness. Thiopental sodium may be useful in neurosurgical patients with increased ICP (reduces MBF and cerebral oxygen consumption - PM02), with occlusion of intracranial vessels, i.e. with focal ischemia.
The cardiovascular effects of drugs are determined by the method of administration and, with intravenous injection, depend on the dose used, as well as on the initial circulating blood volume (CBV), the state of the cardiovascular and autonomic nervous systems. In normovolemic patients, after administration of an induction dose, a transient decrease in blood pressure occurs by 10-20% with a compensatory increase in heart rate by 15-20/min. The main reason is peripheral venodilation, which is the result of depression of the vasomotor center of the medulla oblongata and a decrease in sympathetic stimulation from the central nervous system. Dilatation of capacitance vessels and a decrease in venous return cause a decrease in cardiac output (CO) and blood pressure. Myocardial contractility is reduced to a lesser extent than with the use of inhalational anesthetics, but more than with the use of other intravenous anesthetics. Possible mechanisms are considered to be effects on transmembrane calcium current and nitric oxide uptake. The baroreflex changes slightly, and heart rate increases as a result of hypotension more significantly with methohexital than with sodium thiopental. An increase in heart rate leads to increased oxygen consumption by the myocardium. OPSS usually does not change. In the absence of hypoxemia and hypercarbia, rhythm disturbances are not observed. Higher doses have a direct effect on the myocardium. The sensitivity of the myocardium to catecholamines decreases. In rare cases, cardiac arrest may occur.
Barbiturates constrict cerebral vessels, reducing MBF and ICP. Blood pressure decreases to a lesser extent than intracranial pressure, therefore, brain perfusion does not change significantly (CPP usually even increases). This is extremely important for patients with elevated ICP.
The degree of PM02 is also dose dependent and reflects a decrease in neuronal, but not metabolic, oxygen demand. The concentrations of lactate, pyruvate, phosphocreatine, adenosine triphosphate (ATP), and glucose do not change significantly. A true reduction in the brain's metabolic oxygen demand is only achieved by inducing hypothermia.
After administration of barbiturates during induction intraocular pressure decreases by approximately 40%. This makes their use safe for all ophthalmic interventions. Use of suxamethonium returns intraocular pressure to original level or even exceeds it.
Barbiturates reduce basal metabolism and lead to heat loss due to vasodilation. A decrease in body temperature and impaired thermoregulation may be accompanied by postoperative shivering.
The effects of drugs depend on the dose, rate of administration and quality of premedication. Like other anesthetics, barbiturates cause a decrease in the sensitivity of the respiratory center to the natural stimulants of its activity - CO2 and O2. As a result of this central depression, the depth and frequency of respirations (RR) decrease until apnea. Normalization of ventilation parameters occurs faster than restoration of the respiratory center's response to hypercapnia and hypoxemia. Cough, hiccups and myoclonus make pulmonary ventilation difficult.
The pronounced vagotonic effect of barbiturates in some cases can cause hypersecretion of mucus. Laryngospasm and bronchospasm are possible. Typically, these complications arise when installing an airway (endotracheal tube, laryngeal mask) against the background of superficial anesthesia. It should be noted that during induction with barbiturates, laryngeal reflexes are suppressed to a lesser extent than after administration of equivalent doses of propofol. Barbiturates suppress the protective mechanism of mucociliary clearance of the tracheobronchial tree (TBT).
Induction of anesthesia with barbiturates does not have a significant effect on liver and gastrointestinal function in healthy patients. Barbiturates, by increasing the activity of the vagus nerve, increase the secretion of saliva and mucus in the gastrointestinal tract. Hexobarbital suppresses intestinal motor activity. Nausea and vomiting are rare when used on an empty stomach.
By lowering systemic blood pressure, barbiturates may decrease renal blood flow, glomerular filtration, and tubular secretion. Adequate infusion therapy and correction of hypotension prevent clinically significant effects of barbiturates on the kidneys.
Thiopental sodium reduces plasma cortisol concentrations. However, unlike etomidate, it does not prevent adrenocortical stimulation resulting from surgical stress. Patients with myxedema show increased sensitivity to sodium thiopental.
Barbiturates do not affect the neuromuscular junction and do not cause muscle relaxation. In high doses, they reduce the sensitivity of the post-synaptic membrane of the neuromuscular synapse to the action of acetylcholine and reduce the tone of skeletal muscles.
Barbiturates can induce liver microsomal enzymes involved in their own metabolism. Such self-induction is a possible mechanism for the development of tolerance to them. But acute tolerance to barbiturates precedes the development of enzyme induction. Tolerance, expressed to the maximum extent, leads to a sixfold increase in the need for drugs. Tolerance to the sedative effect of barbiturates develops faster and more pronounced than to the anticonvulsant.
Cross-tolerance to sedative-hypnotics cannot be ruled out. This must be taken into account in connection with the known urban abuse of these drugs and the prevalence of polydrug addiction.
As weak acids, barbiturates are absorbed very quickly from the stomach and small intestine. At the same time, sodium salts are absorbed faster than free acids such as barbital and phenobarbital.
Barbamil, hexobarbital, methohexital and sodium thiopental can be administered intramuscularly. Barbital is also administered rectally in the form of enemas (preferably in children). Methohexital, sodium thiopental and hexobarbital can also be administered rectally as a 5% solution; the action develops more slowly.
The main route of administration of barbiturates is i.v. The speed and completeness of penetration of drugs through the blood-brain barrier (BBB) are determined by their physicochemical characteristics. Drugs with a smaller molecular size, greater lipid solubility and a lower degree of binding to plasma proteins have greater penetrating ability.
The fat solubility of barbiturates is determined almost entirely by the fat solubility of the non-ionized (non-dissociated) part of the drug. The degree of dissociation depends on their ability to form ions in an aqueous environment and on the pH of this environment. Barbiturates are weak acids with a dissociation constant (pKa) slightly above 7. This means that when physiological values Blood pH approximately half of the drug is in a non-ionized state. With acidosis, the ability of weak acids to dissociate decreases, which means that the non-ionized form of the drug increases, i.e. the form in which the drug is able to penetrate the BBB and have an anesthetic effect. However, not the entire amount of non-ionized drug penetrates into the central nervous system. A certain part of it binds to plasma proteins; this complex, due to its large sizes loses the ability to pass through tissue barriers. Thus, a decrease in dissociation and a simultaneous increase in binding to plasma proteins are processes that counteract each other.
Due to the presence of a sulfur atom, thiobarbiturates bind to proteins more strongly than oxybarbiturates. Conditions leading to a decrease in the binding of drugs to proteins (with cirrhosis of the liver, uremia, in newborns) can cause increased sensitivity to barbiturates.
The distribution of barbiturates is determined by their lipid solubility and tissue blood flow. Thiobarbiturates and methohexital are easily soluble in fat, so their effect on the central nervous system begins very quickly - in about one forearm-brain circulation cycle. In a short period of time, the concentration of drugs in the blood and brain is balanced, after which their further intensive redistribution to other tissues occurs (Vdss is the volume of distribution in an equilibrium state), which determines the decrease in the concentration of drugs in the central nervous system and the rapid cessation of the effect after a single bolus. Due to the fact that during hypovolemia, the blood supply to the brain does not decrease as much as to muscles and adipose tissue, the concentration of barbiturates in the central chamber (blood plasma, brain) increases, which determines a greater degree of cerebral and cardiovascular depression.
Thiopental sodium and other barbiturates accumulate well in adipose tissue, but this process develops slowly due to poor perfusion of adipose tissue. At repeated administrations or extended infusion muscle and adipose tissue are largely saturated with drugs, and their return into the blood is delayed. The end of the action of the drug becomes dependent on the slow process of drug absorption by adipose tissue and on its clearance. This leads to a significant increase in half-life, i.e. the time required to reduce the plasma concentration of the drug by half. The presence of large fat deposits helps to prolong the effect of barbiturates.
Due to the fact that barbiturates are weak acids, acidosis will increase their non-ionized fraction, which is more fat-soluble than ionized and therefore penetrates the VAT more quickly. Thus, acidosis enhances, and alkalosis reduces, the severity of the effect of barbiturates. But respiratory changes in blood pH, unlike metabolic ones, are not accompanied by such significant changes in the degree of ionization and the ability of drugs to penetrate the BBB.
Metabolism of oxybarbiturates occurs only in the endoplasmic reticulum of hepatocytes, and thiobarbiturates are metabolized to some extent outside the liver (probably in the kidneys, central nervous system). Barbiturates undergo side chain oxidation at the 5th carbon position. The resulting alcohols, acids and ketones are usually inactive. Oxidation occurs much more slowly than redistribution into tissue.
By oxidation of the side chain at C5, desulfurization of the C2 position and hydrolytic opening of the barbituric ring, sodium thiopental is metabolized to hydroxythiopental and unstable carboxylic acid derivatives. When large doses are used, desulfurization may occur before pentobarbital is formed. The rate of metabolism of sodium thiopental after a single administration is 12-16% per hour.
Methohexital is metabolized by demethylation and oxidation. It decomposes faster than sodium thiopental due to its lower fat solubility and greater availability for metabolism. Oxidation of the side chain produces inactive hydromethohexital. Protein binding of both drugs is quite significant, but the clearance of sodium thiopental is less due to the lower degree of hepatic extraction. Due to the fact that T1/2p is directly proportional to the volume of distribution and inversely proportional to clearance, the difference in T1/2(3 between sodium thiopental and methohexital is associated with the rate of their elimination. Despite the threefold difference in clearance, the main factor in the end of the effect of the induction dose of each of The drug is a process of redistribution. 30 minutes after administration, less than 10% of these barbiturates remain in the brain, after about 15 minutes their concentrations in the muscles are balanced, after 30 minutes their content in adipose tissue continues to increase, reaching a maximum after 2.5 hours. Full recovery psychomotor functions are determined by the metabolic rate and occur faster after administration of methohexital than sodium thiopental. In addition, the hepatic clearance of methohexital, compared with thiopental sodium, is more dependent on systemic and hepatic blood flow. The pharmacokinetics of hexobarbital are close to those of sodium thiopental.
Hepatic clearance of barbiturates may be affected by impaired liver function due to disease or age, inhibition of microsomal enzyme activity, but not by hepatic blood flow. Induction of microsomal enzymes under the influence of external factors, for example in smokers or residents of large cities, can lead to increased requirements for barbiturates.
Barbiturates (except phenobarbital) are excreted unchanged in small quantities (no more than 1%). Water-soluble glucuronides of metabolites are excreted mainly by the kidneys through glomerular filtration. Thus, renal dysfunction does not significantly affect the elimination of barbiturates. Although the volume of distribution does not change with age, the rate of transition of sodium thiopental from the central sector to the peripheral sector is slowed (by approximately 30%) in the elderly and elderly compared with younger adults. This slowdown in intersectoral clearance creates greater concentration Drugs in plasma and brain, providing a more pronounced anesthetic effect in elderly people.
The plasma barbiturate concentration required to switch off consciousness does not change with age. In children, protein binding and volume of distribution of sodium thiopental do not differ from those in adults, but T1/2 is shorter due to faster hepatic clearance. Therefore, the restoration of consciousness in infants and children occurs faster. During pregnancy, T1/2 increases due to better binding to proteins. T1/2 is prolonged in obese patients due to greater distribution into excess fat deposits.
Barbiturates are contraindicated in case of individual intolerance, in case of organic diseases of the liver and kidneys, accompanied by severe insufficiency, in case of familial porphyria (including latent). They should not be used for shock, collapse, or severe circulatory failure.
Long-term use of any sedative-hypnotic drugs can cause physical dependence. The severity of the syndrome will depend on the dose used and the rate of elimination of the particular drug.
Physical dependence on barbiturates is closely related to tolerance to them.
Barbiturate withdrawal syndrome resembles alcohol withdrawal (anxiety, tremors, muscle twitching, nausea, vomiting, etc.). In this case, convulsions are a rather late manifestation. Withdrawal symptoms can be alleviated by prescribing a short-acting barbiturate, clonidine, or propranolol. The severity of the withdrawal syndrome depends on the rate of elimination. Thus, barbiturates with slow elimination will have a delayed and milder clinical picture of withdrawal symptoms. However, abruptly stopping even small doses of phenobarbital to treat epilepsy can lead to major seizures.
Barbiturates are generally well tolerated. The occurrence of side effects and toxicity of barbiturates is mainly associated with their overdose and the administration of concentrated solutions. The most common side effects of barbiturates are dose-dependent circulatory and respiratory depression, as well as initial CNS excitation during induction - a paradoxical effect. Pain during injection and anaphylactic reactions are less common.
The paradoxical effect of barbiturates develops when the inhibitory effects of the central nervous system are suppressed and is manifested by mild excitation in the form of muscle hypertonicity, tremor or twitching, as well as coughing and hiccups. The severity of these symptoms is greater with methohexital than with sodium thiopental, especially if the dose of the former exceeds 1.5 mg/kg. Excitation is eliminated by deepening the anesthesia. In addition, stimulant effects are minimized by pre-administration of atropine or opioids and enhanced by premedication with scopolamine or phenothiazines.
An overdose of barbiturates is manifested by increasing symptoms of depression of consciousness up to coma and is accompanied by depression of blood circulation and respiration. Barbiturates do not have specific pharmacological antagonists for the treatment of overdose. Naloxone and its analogues do not reverse their effects. Analeptic drugs (bemegride, etimizol) were used as an antidote to barbiturates, but it was later found that the likelihood of them causing unwanted effects exceeds their usefulness. In particular, in addition to the “awakening” effect and stimulation of the respiratory center, bemegride stimulates the vasomotor center and has convulsive activity. Etimizole stimulates hemodynamics to a lesser extent, does not have convulsive activity, but lacks “awakening” activity and even enhances the effect of anesthetics.
Allergic reactions with the use of oxybarbiturates are rare and may include itching and a transient urticarial rash on the upper part of the body. chest, neck and face. After induction with thiobarbiturates allergic reactions are observed more often and manifest themselves in the form of urticaria, facial swelling, bronchospasm and shock. In addition to anaphylactic reactions, anaphylactoid reactions occur, although less frequently. Unlike oxybarbiturates, sodium thiopental and especially thiamylal cause a dose-dependent release of histamine (within 20%), but this rarely occurs clinical significance. In most cases, patients have an allergic history.
Severe allergic reactions to barbiturates are rare (1 in 30,000 patients) but are associated with high mortality. Therefore, treatment should be vigorous and include the administration of epinephrine (1 ml in a dilution of 1: 10,000), infusion of fluids, as well as theophylline to relieve bronchospasm.
Interestingly, about a third of adult patients of both sexes (especially young ones) report the appearance of a bulbous or garlicky odor and taste when administered sodium thiopental. Injection of barbiturates into large veins of the forearm is usually not accompanied by pain. But when injected into small veins back side hand or wrist, the frequency of pain with methohexital injection is approximately twice as high as with sodium thiopental injection. The likelihood of venous thrombosis is higher when using concentrated solutions.
The issue of inadvertent injection of barbiturates into an artery or under the skin is extremely important. If a 1% solution of oxybarbiturates is injected into an artery or under the skin, moderate local discomfort may occur without undesirable consequences. But if more concentrated solutions or thiobarbiturates are administered extravasally, pain, swelling and redness of the tissue at the injection site and widespread necrosis may occur. The severity of these symptoms depends on the concentration and total amount of drugs administered. Erroneous intra-arterial administration of concentrated solutions of thiobarbiturates causes intense arterial spasm. This is immediately followed by intense burning pain from the injection site to the fingers, which can persist for hours, as well as paleness. Under anesthesia, patchy cyanosis and darkening of the limb may be observed. Subsequently, hyperesthesia, edema, and limited mobility may occur. These manifestations characterize chemical endarteritis with a depth of damage from the endothelium to the muscle layer.
In the most severe cases, thrombosis, gangrene of the limb, and nerve damage develop. In order to relieve vascular spasm and dilute the barbiturate, papaverine (40-80 mg in 10-20 ml) is injected into the artery saline solution) or 5-10 ml of 1% lidocaine solution. Sympathetic blockade (of the stellate ganglion or brachial plexus) can also reduce spasm. The presence of a peripheral pulse does not exclude the development of thrombosis. Prevention of thrombosis can be facilitated by intra-arterial administration of heparin and corticosteroids followed by their systemic administration.
With prolonged administration, barbiturates stimulate an increase in the level of microsomal liver enzymes. This is clearly evident when prescribing maintenance doses and is most pronounced when using phenobarbital. Stimulation of mitochondrial enzymes also occurs. As a result of activation of 5-aminolevulinate synthetase, the formation of porphyrin and heme is accelerated, which can aggravate the course of intermittent or familial porphyria.
On the contrary, with prolonged use, barbiturates cause the induction of microsomal liver enzymes and affect the kinetics of drugs metabolized with the participation of the cytochrome P450 system. Thus, they accelerate the metabolism of halothane, oral anticoagulants, phenytoin, digoxin, drugs containing propylene glycol, corticosteroids, vitamin K, bile acids, but slow down the biotransformation of tricyclic antidepressants.
Typically, barbiturates are used to induce anesthesia. Any other IV and/or inhalational anesthetics can be used to maintain anesthesia. Barbiturates, when used with BD or opioids, provide a mutual reduction in the needs of each drug separately. They also work well with muscle relaxants.
The use of other anesthetics and opioids in combination with barbiturates for induction increases the degree of circulatory depression and the likelihood of apnea. This should be taken into account in weakened, depleted patients, elderly patients, with hypovolemia and concomitant cardiovascular diseases. The hemodynamic effects of barbiturates are significantly enhanced by the action of propranolol. Radiocontrast drugs and sulfonamides, displacing barbiturates from binding to plasma proteins, increase the proportion of the free fraction of drugs, enhancing their effects.
The combined use of barbiturates with drugs that have a similar effect on hemodynamics (for example, propofol) is not advisable. Sodium thiopental should not be mixed with acidic solutions of other drugs, as this may cause precipitation (for example, with suxamethonium, atropine, ketamine, iodides).
Like all other anesthetics, barbiturates should not be used by persons not specifically trained and without the ability to provide ventilation support and relieve cardiovascular changes. When working with barbiturates, the following factors must be considered:
Barbiturates are drugs that act as central nervous system depressants, and therefore can produce a wide range of effects, from mild sedation to complete anesthesia. They are also effective as anxiolytics, hypnotics and anticonvulsants. Barbiturates also have analgesic effects; however, these effects are somewhat weak, so barbiturates are not used in surgery in the absence of other analgesics (opioids and volatile anesthetics such as halothane). They have the potential to develop addiction, both physical and psychological. In routine medical practice, barbiturates have already been largely replaced by benzodiazepines - for example in the treatment of anxiety and insomnia - mainly because benzodiazepines are significantly less dangerous and there is no specific antidote for barbiturate overdose. However, barbiturates are still used for general anesthesia, in the treatment of epilepsy, acute migraines and headaches (in drugs such as Fioricet and Fiorinal) (under strict supervision and supervision to prevent dependence and abuse), and ( in countries where it is legal) for assisted suicide and euthanasia. Barbiturates are derivatives of barbituric acid.
Barbiturates, such as phenobarbital, were previously used as tranquilizers and hypnotics, but today they have largely been replaced by benzodiazepines due to the lower risk of fatal overdose. However, barbiturates are still used as anticonvulsants, para-operative sedatives (eg, sodium thiopental), and analgesics for the treatment of headaches/migraines (eg, Fioricet).
High doses of barbiturates are used in physician-assisted suicide and, in combination with a muscle relaxant, are used for euthanasia and execution by lethal injection. Barbiturates are often used in veterinary medicine as euthanasia agents for small animals. Sodium thiopental is an ultra-short-acting barbiturate marketed as sodium pentothal. It is often mistaken for "truth serum" or sodium amytal, an intermediate-acting barbiturate that is used for sedation and to treat insomnia, but is also used in so-called "interviews" where the person being asked questions will be more inclined to tell the truth under pressure. the effect of this drug. When dissolved in water, sodium amytal can be ingested, or it can be administered by intravenous injection. The drug itself does not force people to tell the truth, but, presumably, reduces inhibitory processes and slows down creative thinking, making it more likely that people will be “caught off guard” during interrogation and give out information under the influence of emotions. The drug's effects on memory loss and cognitive impairment are thought to reduce a person's ability to invent and remember lies. This practice is no longer considered legally acceptable for use in court due to the fact that the person undergoing such interrogation may form false memories, which reduces the reliability of all information obtained through such methods. However, sodium amytal continues to be used in some circumstances by defense and law enforcement agencies as a "humane" alternative to torture interrogation if the individual is believed to have information of importance to the security of the nation or agency using the tactic.
Taking barbiturates is associated with risks for older adults, pregnant women, and children. As a person ages, their body becomes less able to eliminate barbiturates. As a result, people over the age of sixty-five have increased risk experience harmful effects barbiturates, including drug addiction and accidental overdose. When barbiturates are taken during pregnancy, the drug passes through the mother's bloodstream to the fetus. After birth, the baby may experience withdrawal symptoms and difficulty breathing. In addition, nursing mothers taking barbiturates may pass the drug to their children through breast milk. A rare side effect of barbiturates is Stevens-Johnson syndrome, which primarily affects the mucous membranes.
With regular use of barbiturates, tolerance to their effects develops. As with all GABAergic drugs, withdrawal of barbiturates produces potentially fatal effects such as seizures, as in alcoholic delirium and benzodiazepine withdrawal, however, the more direct mechanism of GABA agonism makes barbiturate withdrawal more severe than alcohol or benzodiazepine withdrawal (making barbiturates one of the most dangerous substances in terms of addiction). Like benzodiazepines, long-acting barbiturates produce less severe withdrawal symptoms than short- and ultra-short-acting barbiturates. Withdrawal symptoms depend on the dose. Users using barbiturates in large doses suffer more than those using low doses. Pharmacological treatment of barbiturate withdrawal is a lengthy process that involves switching the patient to a benzodiazepine. long acting(for example, ) followed by a slow dose reduction. Mental dependence to barbiturates can in some cases last for months or years, and experts strongly recommend dependent people undergoing psychological consultations and participating in group supportive therapy. Patients should not attempt to stop taking barbiturates alone without consulting a physician due to the high mortality rate and relatively sudden onset of withdrawal. Sudden discontinuation may result in severe neurological impairment, physical injury from seizures, and even death due to glutamatergic excitotoxicity.
Symptoms of overdose usually include lethargy, incoordination, difficulty thinking, slowed speech, poor judgment, drowsiness, shallow breathing, staggering, and, in severe cases, coma or death. The lethal dose of barbiturates varies greatly with the development of tolerance and different people may be different. Lethal dose varies greatly among different members class of super-potent barbiturates such as phenobarbital, being potentially fatal in significantly lower doses than less potent barbiturates such as Butalbital. Even in a hospital setting, the development of tolerance is still a problem, since if you stop taking it after the onset of addiction, dangerous and unpleasant symptoms withdrawal symptoms. Tolerance to the anxiolytic and sedative effects of barbiturates usually develops more quickly than tolerance to their effects on smooth muscle , breathing and heart rate, making them unsuitable for long-term psychiatric use. Tolerance to anticonvulsant effects tends to be more correlated with tolerance to physiological effects, however, this means that barbiturates are still a viable option for long-term treatment of epilepsy. Overdose of barbiturates along with the use of other CNS (central nervous system) depressants (eg, alcohol, opiates, benzodiazepines) is even more dangerous due to the development of severe CNS dependence and respiratory depression. When taken concomitantly with benzodiazepines, barbiturates are not only associated with addiction, but also increase the affinity of the benzodiazepine binding site, which enhances the effects of the benzodiazepines. (for example, if benzodiazepines increase the frequency of channel opening by 300%, and barbiturates increase the duration of their opening by 300%, then the combined effects of the drugs increase the overall functionality of the channels by 900%, not 600%). Longer-acting barbiturates have a half-life of 1 day or more. Such drugs subsequently bioaccumulate in the body. The therapeutic and recreational effects of long-acting barbiturates wear off much faster than the drug can be eliminated from the body, allowing the drug to reach toxic blood concentrations after repeated use (even when used at therapeutic doses) despite the user feeling little or even its absence from the drug in the blood plasma. People who use alcohol or other sedatives after the drug has stopped working, but before it is cleared from the body, may experience enhanced effects of other sedatives, which may cause incapacitation or even death. Barbiturates cause an increase in a number of hepatic CYP enzymes (especially CYP2C9, CYP2C19 and CYP3A4), resulting in increased effects of many prodrugs and decreased effects of drugs that are metabolized by these enzymes to inactive metabolites. This can lead to fatal overdoses from drugs such as codeine, tramadol and carisoprodol, which become significantly more potent after being metabolized by CYP enzymes. Despite the fact that all known drugs of this class have the appropriate enzyme induction capabilities, the degree of inhibition in general, as well as the effect on each specific enzyme, covers a fairly wide spectrum. Phenobarbital and secobarbital are the most potent enzyme inducers, while butalbital and talbutal are the weakest enzyme inducers in this class of drugs. The following people died as a result of barbiturate overdose: Judy Garland, Marilyn Monroe, Dorothy Dandridge, Charles Boyer, Ellen Wilkinson, Dalida, Carol Landis, Dorothy Kilgallen, Jean Seberg, Jimi Hendrix, Edie Sedgwick, Phyllis Hyman, Inger Stevens, Kenneth Williams and C.P. . Ramanujam. Ingeborg Bachmann may have died from the effects of barbiturate withdrawal.
Recreational users report that barbiturates give them a feeling of calm contentment and euphoria. With frequent use, physical and psychological dependence may develop. Other effects of barbiturate intoxication include drowsiness, horizontal and vertical nystagmus, slurred speech and ataxia, reduction of anxiety, reduction of internal inhibitions. Barbiturates are also used to relieve negative consequences or withdrawal symptoms following drug use, similar to long-acting benzodiazepines such as diazepam and clonazepam. Drug addicts prefer short-acting and intermediate-acting barbiturates. The most popular are amobarbital (Amytal), phenobarbital (Nembutal) and secobarbital (Seconal). Also widely used combination drug Tuinal (a combination of amobarbital and secobarbital). Short acting barbiturates and average duration actions are usually prescribed as sedatives and hypnotics. These tablets begin to work fifteen to forty minutes after swallowing and the effects last for five to six hours.
Barbiturates act as positive allosteric modulators and, at higher doses, as GABAA receptor agonists. GABA is the main inhibitory neurotransmitter in the central nervous system of mammals. Barbiturates bind to the GABA receptor at several homologous transmembrane sites located at subunit interfaces, which are binding sites distinct from GABA itself and also distinct from the benzodiazepine binding site. Like benzodiazepines, barbiturates potentiate the action of GABA at this receptor. In addition to this GABAergic effect, barbiturates also block AMPK and kainate receptors, subtypes of the ionotropic glutamate receptor. Glutamate is the main excitatory neurotransmitter in the central nervous system in mammals. The simultaneous potentiation of inhibitory GABAA receptors and inhibition of excitatory AMPK receptors explains the powerful relaxing effect of these substances compared to alternative drugs GABA potentiators such as benzodiazepines and quinazolinones. At higher concentrations, they inhibit Ca2+-dependent release of neurotransmitters such as glutamate by affecting voltage-gated calcium channels P/Q type. Barbiturates produce their pharmacological effects by increasing the duration of opening of the chloride ion channel at the GABAA receptor (which increases the potency of GABA), while benzodiazepines increase the frequency of opening of the chloride ion channel at the GABAA receptor (which increases the potency of GABA). Direct opening of the chloride ion channel is responsible for the increased toxicity of barbiturates compared to benzodiazepines in overdose. In addition, barbiturates are relatively nonselective compounds that bind to a whole superfamily of ligand-gated ion channels, of which the GABA receptor channel is only one of several members. This superfamily of ion channels includes the neural nACh receptor channel, the 5-HT3 receptor channel, and the glycine receptor channel. However, while barbiturates (and other general anesthetics) increase GABA receptor currents, these compounds block ligand ion channels, which are predominantly permeable to cation ions. For example, neuronal nAChR channels are blocked by clinically significant anesthetic concentrations of thiopental and phenobarbital. Such findings suggest that (non-GABAergic) ligand ion channels, such as the neuronal nAChR channel, are involved in some of the (side) effects of barbiturates. This mechanism is responsible for the (mild to moderate) analgesic effect of high doses of barbiturates when used at anesthetic concentrations.
In the 1940s, World War II servicemen in the southern Pacific Ocean So-called "Goofballs" (sleeping pills) were given so that soldiers could calmly endure hot and humid climatic conditions. Goofballs helped reduce the body's need for oxygen and also maintained blood pressure, which was important in extreme conditions. Many soldiers returned home with addictions that required months of rehabilitation before discharge. This led to drug addiction problems in the 1950s and 1960s. In the 1950s and 1960s, the amount of published information on barbiturate overdose and dependence increased. Ultimately, this led to barbiturates becoming controlled substances. In the United States, the Controlled Substances Act of 1970 classifies several barbiturates as controlled substances—and they are so classified as of September 2015. Barbital, methylphenobarbital, also known as mephobarbital (brand Mebaral) and phenobarbital are in Schedule IV, and "any substance containing any quantity of any derivative of barbituric acid, or any salt of a derivative of barbituric acid" (all other barbiturates) are in Schedule III . Under the original version of the Act, none of the barbiturates were placed in Schedule I, II, or V; however, amobarbital, pentobarbital, and secobarbital are Schedule II controlled substances unless they are in suppository dosage form. In 1971, the Convention on Psychotropic Substances was signed in Vienna. The 34th version of the treaty, dated January 25, 2014, is intended to regulate amphetamines, barbiturates and other synthetic substances and classifies secobarbital in schedule II, amobarbital, butalbital, cyclobarbital and pentobarbital in schedule III, and allobarbital, barbital, butobarbital, mephobaobital, phenobarbital, butabaobital and vinylbital as a Schedule IV controlled substance (“Green List”). The compound drug Fioricet (butalbital), however, is specifically exempt from controlled substance status, while the similar compound Fiorinal (in which paracetamol is replaced) remains on Schedule III.
In 1988, synthesis and studies on the binding of barbiturates with 6 additional hydrogen bonds to an artificial receptor were published. Since this first article, various types of receptors have been developed, as well as various barbiturates and cyanurates, with no regard to their effectiveness as medicines, and regarding their application in supramolecular chemistry, in the concept of materials and molecular devices. Sodium barbital and barbital are buffer components of the traditional Veronal buffer, which is widely used for serum agarose gel electrophoresis.
Barbituric acid was first synthesized on November 27, 1864 by the German chemist Adolf von Baeyer. This was done by condensing urea (an animal waste product) with diethyl malonate (an ester derived from malic acid). There are several versions of how the substance got its name. The most likely version is that Bayer and his colleagues went to celebrate their opening in a tavern, where the city’s artillery garrison also celebrated the feast of St. Barbara, the patroness of artillerymen. An artillery officer advised that the new substance be christened by combining the name “Barbara” with the word “urea.” Another version is that Bayer synthesized the substance from the urine of a Munich waitress named Barbara. A substance that has medical significance, was discovered, however, only in 1903, when two German scientists working at Bayer, Emil Fischer and Joseph von Mehring, discovered that barbital was very effective in calming dogs. Barbital was introduced to the market by Bayer under the trade name Veronal. It is believed that Mehring suggested the name because the Italian city of Verona was the most peaceful place he knew. It was not until the 1950s that the potential of barbiturates to cause behavioral disorders and physical dependence was recognized. Barbituric acid itself has no direct effect on the central nervous system, and chemists have identified more than 2,500 derivative compounds that are pharmacologically active. The broad class of barbiturates is divided into groups, which are classified depending on the speed of onset of effects and duration of action. Ultra-short-acting barbiturates are commonly used for anesthesia because their very short duration of action allows for better control of the effects. These properties allow doctors to use barbiturates in cases of emergency surgery. Doctors can also quickly bring the patient out of anesthesia if complications arise during surgery. The two middle classes of barbiturates are often combined into a class called "short/intermediate-acting barbiturates." These barbiturates are also used for anesthesia and are also sometimes prescribed for anxiety or insomnia. This is not often practiced today; due to the dangers of long-term use of barbiturates, they have been replaced by benzodiazepines. The last class of barbiturates is known as "long-acting barbiturates" (the most notable of which is phenobarbital, which has a half-life of approximately 92 hours). This class of barbiturates is used almost exclusively as anticonvulsants, although in rare cases they are prescribed for daytime relaxation. Barbiturates in this class are not used for insomnia because, due to their extremely long half-life, the patient will wake up with a residual "hangover" effect and feel sluggish. Barbiturates in most cases can be used either as the free acid or as a salt of sodium, calcium, potassium, magnesium, lithium, etc. Salts of barbituric acid based on codeine and ethylmorphine were developed. In 1912, Bayer introduced another barbituric acid derivative, phenobarbital, under the brand name Luminal, as a sedative hypnotic.
Previously, barbiturates were widely prescribed as sedatives and hypnotics. Currently, the scope of their use is significantly limited, since, firstly, they have a narrow therapeutic scope, which can lead to overdose and toxic effects, and secondly, with long-term use of barbiturates, addiction and drug dependence may develop.
Many sedatives, including chloroform, chloral hydrate, and paraldehyde, were introduced into medicine in the nineteenth century. The first barbiturate was discovered in the laboratories of the German chemist Adolf Bayer in Munich in 1862.
The effects of various barbiturates are generally consistent, but they do vary in magnitude and duration of action. Barbiturates are classified into the following types: ultra-short and short-acting, medium-lasting and long-acting. For example, pentobarbital and secobarbital are strong, fast-acting drugs (lasting two to four hours), amobarbital is a medium-acting drug (six to eight hours), and phenobarbital is a long-acting drug (eight to ten hours).
Barbiturates have a dose-dependent depressant effect on the central nervous system: from a state of mild sedation to coma. Currently, their use is limited: they are prescribed as anticonvulsants and drugs for induction of anesthesia.
In moderate doses, barbiturates cause a state of euphoria, close to intoxication. Similar to alcohol, barbiturates can cause loss of coordination, unsteady gait, and slurred speech. Impaired motor coordination and ataxia are associated with inhibition of spinal polysynaptic reflexes and supraspinal regulation. Loss of emotional control and uncontrollable behavior are also typical consequences of barbiturate use and are due to their effect on the limbic system. Anti-anxiety effects and sleep are induced by high doses, and even higher doses cause surgical anesthesia. Barbiturates impair concentration, memory, and learning. May cause fixation amnesia. Vegetotropic effects include an increase in the tone of the vagus nerve, leading to bronchospasm, which is the cause of most deaths associated with the use of barbiturates. This often occurs when intravenous administration sodium thiopental, used for induction of anesthesia. To prevent bronchospasm, M-anticholinergic blockers are used as premedication in this case. In large doses, barbiturates, also due to an increase in the tone of the vagus nerve, have a cardiodepressive effect: they slow down the heart rate and atrioventricular conduction, lower blood pressure and disrupt the activity of the gastrointestinal tract.
Barbiturates were first introduced into medical practice in 1903, when barbital was marketed as Veronal. Soon the drug began to be often used as a sedative and as the first sleeping pill. The use of barbiturates in medicine increased until the 1960s, but declined markedly in subsequent years. The rise and fall of barbiturate use had several causes. Among the many ailments experienced by mankind in the nineteenth century, insomnia and anxiety were the most common. Thus, any drug that combats anxiety or promises sleep for an insomniac has enjoyed enormous popularity and commercial success. Barbiturates did have the ability to induce sleep and combat anxiety - this explained their dominance in the market. However, when long-term use they were addictive and drug dependent, which led to their gradual abandonment in favor of the somewhat safer benzodiazepines.
Veterinarians use pentobarbital as an anesthetic and euthanasia agent.
There are a certain number of problems associated with the use of barbiturates: first of all, the emergence of drug addiction. Barbiturate drug addicts prefer short- or moderate-acting drugs, namely pentobarbital (Nembutal) and secobarbital (Amytal).
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BARBITURATES, substances used as sedatives or hypnotics. They are classified as narcotic drugs; in large doses, as well as in combination with other drugs, such as alcohol or tranquilizers, are quickly addictive and... ... Scientific and technical encyclopedic dictionary
Barbiturates- derivatives of barbituric acid, hypnotic drugs with anticonvulsant effect. Barbituric acid itself does not have hypnotic properties. Barbiturates act in a wide range: from weak sedative effect to coma and death... Encyclopedic Dictionary in psychology and pedagogy
BARBITURATES- A very large group of drugs that belongs to hypnosedatives. Of the more than 2,500 barbiturates that have been synthesized, approximately 15 are currently in use. They are used in different cases, including... ... Dictionary in psychology
A group of organic compounds, derivatives of barbituric acid; widely used as sleeping pills and narcotics. New dictionary foreign words. by EdwART, 2009. barbiturates, units. barbiturate, a, m. (German: Barbituraten). chem., med.... ... Dictionary of foreign words of the Russian language
- (barbiturata) derivatives of barbituric acid; depending on the chemical structure, dose and method of administration, they have a sedative, hypnotic, narcotic or anticonvulsant effect... Large medical dictionary
A group of medicinal substances derived from barbituric acid (See Barbituric acid), which have hypnotic, anticonvulsant and narcotic effects due to their inhibitory effect on the central nervous system.... ... Great Soviet Encyclopedia - (barbiturate) group of sedative-hypnotic drugs, addictive, which are used to relieve anxiety or to help a person fall asleep... General psychology: glossary
