Dose action curve

To determine the dose of a substance, you need to know the magnitude of the effect it produces. Above, you saw that the narcotic effect depends on the dose taken. There may be hundreds of dose sizes, and it would be rather difficult to understand the various effects. Therefore, we need a tool that will present the data clearly and definitely, to the extent possible. In pharmacology, such a tool is a dose action line. This is a common form of image effects obtained from taking different doses. Several groups of people will take different doses of alcohol and after a certain time they will be asked to describe the degree of their relaxation. From the average data for each group, a schedule is compiled, which will be the dose action line.
In fig. 4-2 shows a sample of such a line. Vertical presents the changes of interest to us, let us designate them as the “effect size”. The nature of the changes to which special attention is paid in this book is determined by generally accepted methods for measuring the mood, behavior or functioning of the nervous system. Examples are memory testing, mood assessment, measurement of physiological parameters such as pulse. Doses are marked on the horizontal axis (often their logarithms). The studies cover at least three doses. After that, it remains to plot the data on the strength of the effect of the studied drug on people who have received a certain dose. Either different doses are given to different groups of people, or the same group receives these doses over several days.In both cases, we get the average effect of each dose studied.

Thus, the graph depicts the functional dependence of the magnitude of the effect on the dose of the drug.
From Figure 4-2, it can be seen that the effect varies with dose change. The shape of the line suggests that an accurate dose is needed to accurately determine the magnitude of the effect. For example, the larger the dose of the drug in Figure 4-2, the greater the effect it produces. But there is a limit: at the highest doses, the schedule tends to move to a horizontal line. This means that increasing the dose over a certain level does not enhance the effect. You can illustrate this with the effect of alcohol on the time it takes a person to have a simple reaction, for example, say yes or no in response to the presence or absence of any stimulus, say light. For an “average” drinking person, taking two 0.33-liter doses of beer per hour had practically no effect on the reaction time. After four doses, the time required for a response has increased markedly.After five doses, responses began to be given even more slowly. If a person took nine or more doses of beer per hour, he was very sleepy, and thus measuring the further deterioration of the reaction as alcohol was consumed would be simply useless. At this point, when a person has to make great efforts not to disconnect, the possibilities and benefits of such a measurement will tend to zero. After a ninefold dose, the line of action will take a horizontal position on the graph.the possibilities and benefits of such a measurement will tend to zero. After a ninefold dose, the line of action will take a horizontal position on the graph.the possibilities and benefits of such a measurement will tend to zero. After a ninefold dose, the line of action will take a horizontal position on the graph.

This experience with alcohol and the time of a simple reaction shows that the question is not what effect a particular drug produces at all, but how much the effect is at a particular dose.
Variation of dose action lines. Graphs of the effect of dose size may differ from that shown in Figure 4-2. One option is a biphasic narcotic effect. This means that up to a certain point with increasing dose, the effect increases, but then, despite the continued increase in dose, it falls. This case is shown in the figure.
The magnitude of the effect here increases with increasing doses from small to moderate. At higher doses, the line changes direction, noting a decrease in the narcotic effect. In this example, the magnitude of the effect returns almost to the original level obtained at the lowest doses. Pulse is one of the biphasic effects of alcohol and marijuana.

Any drug produces many effects, the strength of which is measurable, and therefore a dose action line can be constructed for any such effects. Many lines have similarities, and as a rule they belong to the type shown in Figure 4-2. Nevertheless, some dose lines of a single drug may look completely different. It depends on what effects to compare with each other.

We know that the line of action of the dose depends on the magnitude of the measured effect. This is illustrated in Figure 4-4, representing the results of laboratory studies of how sexual arousal feelings change in female students (first effect) and physiological parameters (blood flow to the genitals) of their arousal (second effect) when they consume small and moderate doses of alcohol. A negative narcotic effect is also shown on the vertical axis. According to the schedule, with an increase in the dose of alcohol to moderate, the students felt an increase in sexual arousal (large doses were not studied). At the same time, the physiological parameters of female sexual arousal decreased with increasing dose.
Slope, maximum effect and power of action. These are terms used in pharmacology to describe in more detail the action of a drug. They are presented in Figure 4-5, where dose action lines for two drugs, A and B, are constructed. Graphs have a slope, its characteristic is steepness. It is associated with time passing to achieve a strong effect. This inclination is taken into account in practical activities: in drafting a prescription for drugs or predicting life-threatening effects of drugs. An example of the latter is the sedative effect of barbiturates or the effect that the simultaneous use of benzodiazepines and alcohol gives. In Figure 4-5, line A has a steeper slope than line B, and since these curves then take a horizontal direction, this dose of drug A produces a greater effect.

Figure 4-5 also presents two other concepts: maximum effect and strength of action of a drug. The maximum effect of this drug corresponds to the highest point of the dose action line. In the figure, this is the moment when the curves stop growing. In this case, we have two drugs with the same maximum effect. The power of action – the dose of the drug, giving this maximum effect. If you draw a line from the point of maximum effect down to the horizontal axis, the point of intersection will be the force of action of the given drug for a particular effect.

Removing drugs from the body

Drugs can be eliminated directly from the body or first decompose into substances whose metabolites are less likely to be re-absorbed. These secondary substances are also excreted from the body. Liver enzymes play a major role in drug metabolism. It is important that these enzymes are also found in other organs, such as the kidneys and the digestive tract. Therefore, a drug ingested by mouth undergoes partial decomposition by enzymes. Thus, less substance reaches the required place than was accepted. Some drug metabolites are pharmacologically active. They cause, for example, side effects of various drugs. There are two examples of metabolites with psychoactive properties: these are diazepam (Valium) and chlordiazepoxide (Librium) metabolites. One of the metabolites of diazepam is removed from the body more slowly,than diazepam itself. Their action is terminated by further metabolism or elimination from the body along with urine.

The main organ responsible for the removal from the body of both drugs and their metabolites is the kidneys. But removal can go in other ways. For example, drugs ingested by mouth are sometimes excreted along with feces. Drug metabolites can be removed along with bile.
Drugs are released in human milk, and although the quantity of drug withdrawn in this way is small, the infant is at serious risk. Drugs can also be removed through the lungs: this is why the breath of a person who has taken alcohol smells like alcohol. Finally, drugs are removed with sweat. Drug testing Discussion of the process of removing drugs from the body brings us to the question of how to test a person for drugs. There are many methods for determining whether a person has taken drugs using urine or blood tests. Urinalysis is more sensitive because there can be found metabolites of the drug. If the drug is found in the blood, it indicates a very recent use of it.

The success of the test depends on many factors, including the magnitude of the last dose taken, the specific test method and the exact procedure followed. The ability to detect a drug depends mainly on the rate of its elimination from the body and the rate of elimination of its metabolites. Table 4-4 shows the time of excretion of drugs (and their metabolites) from the body and the time after which it is possible to detect them in the body after use. Less time in the second column corresponds to the removal of the drug itself from the body, more time – its metabolites.
For alcohol, only one time is indicated, since its metabolites are widely distributed in the body, and the alcohol test for its metabolites will be unreliable.

The third column indicates the maximum time during which the test can produce results. This time is greatly increased if the content of drug metabolites in the body can be measured. This time is usually much shorter than the period of excretion of drugs and their metabolites from the body. This is because testing has limited sensitivity and cannot detect the content of metabolites after a certain limit. This limit depends on the specific metabolite and testing methodology. This means that a positive review of pharmacokinetics has led you to the result; however, it does not inform us of the exact time of drug use. The exception is, as noted, the detection of a drug in the blood, which indicates a very recent use.Traces of a large dose of marijuana can be detected within eight days of use. In the body of people who constantly use marijuana, you can find traces of it more than a month after taking the last dose.

Farcodynamics 

Let us turn to understanding the mechanism of action of drugs. This is a subject of pharmacodynamics. In the remainder, terms will be introduced in which pharmacologists describe the effects of drugs, as well as graphical expressions of such effects.

Distribution in the body

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The transfer of drugs to the place of their action is strongly influenced by the biochemical properties of both the organism and the drugs. Since the drug is transported by blood, it is natural that those parts of the body that are more supplied with blood receive and more drug. Indeed, after the absorption of a drug, the heart, brain, kidneys, liver and other organs that require a lot of blood receive most of it. To parts of the body in which the blood circulation is not so intense (muscles, internal organs and fatty tissue), the drug comes much later. In addition to circulation, the transmission capacity of the membranes and tissues affects the nature of the spread. Fabrics with higher throughput get the drug faster.

Drug properties have a significant effect on distribution. The main example is solubility in fats. The better the drug dissolves in them, the easier it passes through the shells and quickly reaches its place of action.
The solubility of a substance in fats greatly depends on how much it enters the brain. The volume of blood passing through the brain is so large that the brain could become a real depot of drugs (and other chemicals) entering the body. But before any substance enters the brain, it must overcome the barrier. As mentioned in Chapter 3, this barrier serves as a blood filter, and removes toxins from it before they enter the brain. Filtering is based on the fact that the pores of the capillaries of the brain are very small and close to each other, which makes it impossible for foreign substances to pass through them. In addition, the capillaries are surrounded by a thin wall of glial cells that make up the second line of defense. If the drug is well soluble in fats, like benzodiazepine diazepam (Valium), then it easily passes through the capillaries,and through glial cell membranes. But these obstacles are insurmountable for less fat-soluble substances.

Another chemical property of drugs that affects their distribution is the ability to combine with elements of the body. For example, some drugs, such as barbiturates, interact with certain plasma proteins. The more selectively the drug reacts with the elements of the body, the slower it is transferred to the right place. Likewise, the chemical structure of some drugs makes them susceptible to reaction with the tissue of the body. In this case, the drug can be released from this tissue only after a long time. It may appear in the blood, but its release from adipose tissue is so slow that it has a very minor effect on the psyche. A good example of a drug that reacts with fat is marijuana. Due to the selective nature of the compound with the molecules of the body, it does not spread throughout the body,and its effect is weakened. Part of the dose taken can not quickly reach its place of action.

Thus, the processes of absorption and distribution of the drug show that the drug in the body violates the biochemical equilibrium and causes resonance throughout the system. Absorption and distribution are complex bases of bioavailability, that is, the amount of a drug that reaches its site of action. Bioavailability is very important when considering the effects of drugs on the body. To understand the long-term effects of drugs, you need to trace their destruction or elimination from the body.

Through the skin

In medicine, this method usually replaces the ingestion, if the substance can adversely affect the digestive tract. Acceptance through the skin is not particularly effective for most drugs, because the skin is a barrier to many chemical compounds and is relatively impermeable. But there are drugs that freely penetrate even through intact skin, and for them this method is quite applicable.
The absorption of drugs through the skin can be accelerated by selecting those parts of the body where the skin circulation is strongest. In addition, to improve the penetration of the drug can be mixed with other substances (for example, to make an oil mixture). In the form of a patch, you can take nitroglycerin – this removes the problem of the metabolism of a substance before it reaches its destination.
The choice of method depends on the properties of a particular substance, the purpose of its reception, as well as the advantages and disadvantages of a particular method of taking this substance in these circumstances. In tab. 4-2 are the main considerations for the eight drug intake methods that we discussed above. Table 4-3 shows the intake methods used for some substances.

Absorption of a drug 15

Absorption can also be defined as the rate and extent of a substance leaving a place where it was introduced. It is very important for the action of the drug. Absorption and the factors inactive on it are extremely important because they affect bioavailability. This is the part of the dose taken, reaching the place of its action or falling into the liquid, which will transfer it to its destination. Thus, the bioavailability of a drug is directly related to its effect.
Differences in the rate of absorption for different methods of administration are determined by many factors. Let’s give some examples. In all cases, except for intravenous injection, the drug must pass through at least one of the shell before it begins to spread throughout the body. Since shells are mainly composed of lipids (fats), those drugs that are better dissolved in fats are absorbed much faster. Alcohol is an example of a fat-soluble drug. Another factor is the form in which the drug is injected: it is absorbed faster in aqueous solution than in suspension, in a fat mixture or in solid form. This is due to the fact that in the state of an aqueous solution, it is already completely ready for absorption. The solubility of a substance taken in solid form depends on the conditions in the part of the body where absorption takes place. For example,Aspirin is practically insoluble in the acidic environment of the stomach, which limits the possibility of its absorption. The condition of the digestive tract affects the absorption of substances ingested through the mouth. Strong blood circulation in the place of absorption accelerates it. Finally, the area of ​​the absorbing surface matters: the larger it is, the faster the substances are absorbed into the blood.
The factors affecting absorption are many, and they can act separately or all at once. Therefore, it is very difficult to accurately determine the effect of a drug on a person in certain conditions and at a certain time. Intravenous injection is the most effective way to deliver a drug to the site of its operation: the drug immediately connects with blood, the main element in the distribution system of substances in the body, and therefore many factors that delay absorption do not work.

Dose of the drug

As noted in Chapter 2, the most important thing that determines the effect of a substance entering the body is its quantity (these are components 1 and 2 in table 4-1). Pharmacology dose is determined on the basis of human weight, because the body of a larger person contains more fluid than the body of a smaller one. Consequently, if two such people take the same amount of a drug, then its concentration will be lower in the body (and, accordingly, in the organ on which this substance acts) of a larger person. The greater the content of the drug in one or another part of the body, the, as a rule, the stronger the effect. Therefore, the amount of the substance taken should be accurately calculated based on the weight of the person.
First, determine the desired dose of the drug in milligrams per kilogram of human weight. Then the patient is weighed. Then it is easy to calculate the desired dose for this person. For example, if the required dose is 0.8 mg / kg, a person weighs 80 kg, then he should be given 0.8 x 80 = 6.4 mg of the drug.

Methods of administration

In pharmacology, the expression “method of administration” means exactly how the substance enters the body. The strength of the substance (component 3 of table 4-1) largely depends on the method of administration. In this section, we will discuss eight ways. These are the five most common: oral administration, injection (includes three types – subcutaneous, intravenous and intramuscular) and inhalation. Three other important ways are intranasal (inhalation), sublingual (placement under the tongue) and transdermal (through the skin).
Orally. Swallowing is probably the most familiar way to take medicine. Such drugs come in the form of pills, capsules, powders, liquids. These are a variety of headache medications, cough syrups, cold pills, etc., that are available in every pharmacy. Virtually all of the most affordable medicines are taken by mouth. This is the safest, most convenient, and economical way to take medicine.
After ingestion, the substance enters the stomach and is absorbed in the small intestine. Both the speed and the strength of its action depend on how the substance makes this way. The main factor determining the final effect is the food that is in the digestive tract during the intake of the substance. The more food, the slower the stomach is emptied, and in addition, it can reduce the concentration of the drug. As a result, absorption begins late, and the level of the substance in the blood is low. (This result is clearly noticeable if you compare the degree of intoxication from drinking alcohol after a heavy meal and on an empty stomach.) In addition, food can envelop the substance, and it will be released from the body along with feces. Finally, the substance taken by mouth is absorbed by the blood more slowly than if taken in other ways.

Thus, the advantages of ingestion through the mouth (comparative safety, convenience and economy) are balanced by disadvantages – a long time before absorption and a low efficiency. Moreover, gastric acids released during digestion partially destroy some substances, in particular, heroin. Once in the blood, such altered substances pass through the liver, the main organ responsible for the metabolism of most substances, and therefore only a small part of the substance reaches the brain, which inevitably reduces its effect.

Injection. The basis of the three other most common methods of drug intake is an injection of a substance using a syringe. They are usually dissolved beforehand in a liquid (“carrier”) or mixed with it. Methods of administration associated with the injection of substances subcutaneous, intravenous and intramuscular. Subcutaneous intake Injecting a substance under the skin is the simplest of these three methods, since it suffices to pierce the skin with a needle. This method is used by many novice drug addicts. It is also used in medicine for the introduction into the body of substances that do not irritate tissues (because substances introduced in this way are absorbed gradually and slowly, although faster than when taken by mouth). You can pick up a carrier fluid with which the substance is absorbed into the blood the fastest.The subcutaneous route of administration is not suitable in two cases: if the substance is irritating to the tissue and if too much solution is required to obtain the desired effect.
Intramuscular intake. In order to inject a substance into a muscle, a deeper needle penetration is needed than with a subcutaneous injection. But if the substance injected in this way is dissolved in water, and there is intensive blood circulation in the muscle, it is absorbed faster. The rate of absorption depends on which muscle group is injected. It is also influenced by the type of carrier fluid in which the substance is dissolved. The lack of an intramuscular injection is that it causes pain at the injection site. In addition, such an injection should be done by a specially trained person, otherwise there is a high risk of blood poisoning and tissue damage.

Intravenous intake. This method removes most of the problems associated with absorption. The solution of the substance is injected directly into the vein, and it begins to act immediately. Therefore, this method is used in the provision of emergency medical care. You can enter the exact dose needed by this person. In addition, irritating substances can be administered intravenously (as well as irritating “carriers”), because the walls of blood vessels are relatively insensitive, and the substance also dissolves in the blood.

The benefits of intravenous administration are obvious. The main reason for its relatively rare use is that it is more likely to be associated with possible complications, because a large amount of the substance reaches the target organ very quickly. Another consideration is that if a substance is injected through a vein for a long time, it should be strong and healthy. In general, intravenous injection is associated with the risk that it should be done slowly and monitor the patient’s response. Of course, these requirements are met in a medical institution, but it is unlikely that the same thing happens where people take drugs.
People who regularly take heroin, cocaine or their mixture (“speedball”) intravenously are often referred to as “well-established” drug addicts. They inject the drug into the vein because they want immediate and strong action. The usual dangers of intravenous use in combination with the sudden strong effect of the drug cause a great deal of damage to human health. Today, the fatal outcome of intravenous drug use is common among drug addicts.

To prevent infection by diseases such as AIDS, hepatitis, or tetanus, sterile needles and solutions should be used when injecting drugs intravenously. Drugs introduced into the body in any of the three methods of injection bypass such protective mechanisms as the skin and mucosa. Thus, pathogenic microorganisms that the body cannot neutralize can be brought in with a dirty needle or non-sterile solution. Therefore, street addicts are at great risk of contracting AIDS.

Inhalation. Some drugs can be absorbed through the membranes of the lungs. With inhalation of such drugs, the desired effect is achieved quickly (faster than with subcutaneous or intramuscular injection). In order for the drug to be inhaled, it must be in a certain state. Inhalation is applicable to drugs that can be brought into the gaseous state. For example, you can inhale substances that are components of ordinary and affordable industrial products. Such substances with psychoactive properties are called inhalants. This, for example, benzene, toluene and ligroin. You can inhale drugs that are intended for use in the form of drops. Moreover, it is possible to inhalate a mixture of gas and narcotic with small particles. These are tobacco smoke and crack crack. Inhalation of the drug gives almost complete and rapid absorption.The disadvantage of inhalation is that only small amounts of the substance can be taken at a time.
Inhalation. A powder drug is inhaled through the nose. It is absorbed through the nasal mucosa and sinuses. Cocaine, heroin and snuff are usually taken in this way. Inhalation through the nose is a good way to quickly and completely absorb poorly soluble substances. True, if you inhale an annoying drug, it can disrupt blood circulation and cause serious harm. In this regard, we can give an example of the destructive effects of cocaine on the nasal septum and nasal tissue.

Dissolving under the tongue. A tablet of substance is placed under the tongue and dissolves with saliva. The substance is absorbed through the mucous membrane of the oral cavity. In this way, nitroglycerin is usually taken, used to relieve pain in the heart. This way you can take nicotine in the form of tobacco gum or “raw” powder.

Intake under the tongue gives a faster and more complete absorption of the substance than ingestion. In addition, this way you can take drugs that irritate the stomach and cause vomiting. In the form of pills, you can use almost any substance with narcotic properties. However, this method is less popular than one would expect, because many drugs have an unpleasant taste.

  • Orally
    • One of the safest, most convenient and cost-effective ways to receive.
    • The presence in the stomach of food slows down the absorption and reduces the amount of substance entering the blood.
    • Gastric acids destroy some drugs, and thus reduce their effect.
  • Subcutaneous injection
    • The easiest of the three methods of injection.
    • Absorption is faster than when taken by mouth, but slower than with other types of injections.
    • A good way to take drugs that do not irritate the tissues, because they dissolve slowly and gradually, and the substance has a lasting effect.
    • The method cannot be used if the substance is irritating to the tissue, or if a large volume of fluid is to be injected.
  • Intramuscular injection
    • It requires a deeper penetration into the tissue, but with proper preparation of the solution and the choice of a site with an intensive blood circulation for injection, it gives a faster absorption.
    • Causes pain at the injection site.
    • The use of this method by people without special training is associated with the risk of blood poisoning or tissue damage.
  • Intravenous injection
    • Gives the fastest absorption of all methods of administration.
    • The substance has an immediate effect, so the method is good for emergency medical care.
    • Since the substance acts immediately, you can enter the exact dose needed by a particular person.
    • The best method of injection is for receiving irritating tissue drugs, since the walls of blood vessels are relatively insensitive, and the drug is further dissolved in the blood.
    • Associated with the potential danger that a large amount of the drug will immediately reach the scene of action.
    • Frequent use of this method requires healthy and strong veins.
    • In order to avoid complications, the dose of the substance should be introduced gradually and following the reaction of the person.
  • Inhalation
    • If the drug can be inhaled, it is absorbed almost completely and faster than with subcutaneous or intramuscular injection.
    • At one time you can not enter a large number of substances.
  • Inhalation through the nose
    • If the drug is poorly soluble, it is the best way to take it.
    • Inhalation of a drug that irritates tissue or interferes with blood circulation can cause serious harm.
  • Dissolving under the tongue
    • In principle, this method can take almost any drug (in the form of pills).
    • The substance is absorbed faster and more fully than when ingested.
    • A good way to take drugs that irritate the stomach and cause vomiting.
    • The method is applied less frequently than is possible, since many drugs have an unpleasant taste.
  • Through the skin
    • Alternative to ingestion through the mouth, if the substance is bad for the digestive tract.
    • Many substances cannot be taken in this way, since their skin is relatively poorly permeable.
    • You can speed up absorption by choosing places with the best skin circulation, and improve the penetration of the drug through the skin by mixing it with another substance.

Designer drugs and the brain

Converted, or “designer” drugs – synthetic substances obtained by a slight change in the chemical structure of an already known drug. If the drug retains its ability to act on the receptors, it will still have the desired effect, but it will not be prohibited by law. In other words, a specialist chemist can slightly change the heroin molecule and get a new drug with the same properties. And to pursue the spread of this new compound will be impossible under the law. (However, in 1986, a law was passed in the United States that changed this state of affairs.) Converted drugs reduce the risk of selling them, but not when they are used.

Not so long ago in California, an underground chemical laboratory began producing converted heroin, the so-called MRRR. Due to improper manufacturing technology,instead of heroin MPPP, the toxic substance MPMP was obtained. It turned out after several young drug addicts were hospitalized with complete paralysis. At first, the cause of this epidemic of paralysis was a complete mystery. The symptoms strongly resembled Parkinson’s disease. But only older people are affected. Solve the problem helped the ingenious guess of a doctor named William Langston. He used the drug L-DOPA to treat paralyzed drug addicts. Its use has returned patients at least the ability to talk. After that it turned out that they were the victims of the unfortunate altered heroin.But only older people are affected. Solve the problem helped the ingenious guess of a doctor named William Langston. He used the drug L-DOPA to treat paralyzed drug addicts. Its use has returned patients at least the ability to talk. After that it turned out that they were the victims of the unfortunate altered heroin.But this disease affects only older people. Solve the problem helped the ingenious guess of a doctor named William Langston. He used the drug L-DOPA to treat paralyzed drug addicts. Its use has returned patients at least the ability to talk. After that it turned out that they were the victims of the unfortunate altered heroin.

Studies have shown that MRTR acts selectively, and the main substance of its impact is the black substance. It causes its rapid destruction, and this loss is almost irretrievable. However, the treatment of victims of MRTR showed that the L-DOPA preparation is able to restore some of the black substance cells.
It is necessary to remember two important circumstances. Firstly, the great danger associated with the use of recast drugs is obvious. Since they are not tested on animals and not investigated in the laboratories of medical centers, the person using them is at great risk. Secondly, there may be no obvious symptoms of brain damage. Many people who have taken MRTR only once or twice in their lives do not have any symptoms of Parkinson’s disease. However, the partial destruction of the black substance probably happened. In the process of aging of the body, its cells will collapse further, and this increases the risk that such people will pay for Parkinson’s disease with a single dose of MRTP.

Forebrain

Thalamus and Hypothalamus. From the point of view of studying the effects of drugs, the forebrain, which includes the thalamus, hypothalamus and some other structures, in particular, the cerebral cortex (see Fig. 3-5), is most important for us. The thalamus is often called a relay station, as it receives all the original impulses from the senses and transmits this information to the corresponding parts of the brain. The hypothalamus is the main organ regulating behavior. Obviously, its different parts are responsible for food, drink, body temperature, aggression and sexual behavior. To determine the exact purpose of a particular part of the brain is very difficult, and sometimes we get conflicting data. The main ways to study parts of the brain are damage and stimulation. In a surgical way, some part of the brain of the experimental animal is damaged. After the animal recovers from the operation,there are changes in his behavior that correlate with the damaged part of the brain. For example, damage to one part of the hypothalamus leads to the fact that the animal stops eating, and as a result of the operation in another area, the animal’s appetite is unnaturally increased, which even leads to obesity. Thus, we see that in the hypothalamus there are at least two areas responsible for eating: one regulates the feeling of fullness, the other – the feeling of hunger. Electrical stimulation of areas of the brain, as a rule, has the opposite effectwe see that in the hypothalamus there are at least two areas responsible for eating: one regulates the feeling of fullness, the other – the feeling of hunger. Electrical stimulation of areas of the brain, as a rule, has the opposite effectwe see that in the hypothalamus there are at least two areas responsible for eating: one regulates the feeling of fullness, the other – the feeling of hunger. Electrical stimulation of areas of the brain, as a rule, has the opposite effect damage.

Damage or stimulation of certain parts of the brain also extends beyond them, so that exposure can affect entire transmission channels of nerve impulses. Therefore, it is better to speak not about the centers of hunger, but about the channels of transmission of the corresponding impulses. However, even this approach can be simplified, because some researchers have noticed that not only information about hunger can be transmitted through such channels. So, they also affect the coordination of movements, taste sensations and much more. But be that as it may, all researchers agree that the hypothalamus plays an important role in controlling hunger, thirst, and other basic sensations.
The center of pleasure in the brain Despite these difficulties, electrical stimulation of brain areas was the basis of one of the most significant discoveries in research on the relationship between the brain, behavior and drugs. In the 1950s, psychologist James Olds worked with the brain of a rat, implanting electrodes in various parts of it and studying the effects of their stimulation. When electrically stimulating certain parts of the brain, the rat seemed to have fun. Here’s how Olds describes his discovery:
When the animal entered a certain corner of the cage, I gave him a short discharge of electric current. But the animal did not run away from the corner, but on the contrary, returned there after a short retreat caused by shock from the first stimulation. After the second stimulation, the retreat period was even shorter. By the time of the third electrical discharge, the rat did not go out of the corner.

Conducting further research, Olds and his colleague Milner found that if the electrodes were implanted in certain areas of the brain, especially in the middle forebrain, the rat could even be trained to press a lever in the cell, including electrocution, some neurons of the middle node go beyond its limits and connect it with the lateral part of the hypothalamus. When the rats learned to stimulate this area, they pressed the lever up to a thousand times per hour. This gave reason to assume that the “pleasure center” is being stimulated. Obviously, this part of the brain is the end point of the channels through which information about the desire for pleasure and its reception passes. Accordingly, to understand the properties of drugs to cause a sense of pleasure, it is necessary to study this area of ​​the brain.One of the main channels of transmission of nerve impulses in the median node is dopamine, so the researchers put forward a version that the main chemical substance associated with the property of drugs to bring pleasure is dopamine. This is supported by the success of the next experiment. The rats learned to press a lever that delivers cocaine through a miniature pipette implanted in the median forebrain. Thus, people who use cocaine, change the chemical processes occurring in the system of control over pleasure.implanted in the median forebrain node. Thus, people who use cocaine, change the chemical processes occurring in the system of control over pleasure.implanted in the median forebrain node. Thus, people who use cocaine, change the chemical processes occurring in the system of control over pleasure.

The structure of the forebrain includes three more complex organs: the limbic system, the basal ganglia and the cerebral cortex. These bodies form such inherent only to man areas of mental activity, such as memory, logic, speech, planning and reasoning.
Limbic system. These are several organs located inside the forebrain. One of them, amidal, is responsible for certain types of aggression. Another important organ of the limbic system is the hippocampus (seahorse), an important part of the memory system. People with a damaged hippocampus will remember everything that happened to them before the damage, but they are unable to remember new information. Alcohol abuse in combination with poor nutrition leads to a serious mental disorder, known as Korsakov syndrome. In patients suffering from this disease (usually alcoholics from the lower classes of society), there is a memory disorder that is associated with damage to the hippocampus.
Ganglion. One of the causes of Parkinson’s disease is damage to the ganglion, namely the degeneration of a special group of nerve cells, the so-called “black substance”. These cells produce dopamine for the ganglion, and with their degeneration, less and less dopamine is involved in the transmission of nerve impulses. Interestingly, Parkinson’s disease does not occur as long as at least 20% of the substantia nigra cells remain intact.

Cortex. In fig. 3-4 shows the lobes of the cerebral cortex. The occipital lobe is associated with vision and perceives signals from the optic nerve. The temporal lobe plays an important role in the processing of auditory sensations and, apparently, controls the mechanisms of speech. Damage to the left temporal lobe causes a serious impairment of speech ability (at least if the person is right-handed). Damage to the right temporal lobe often affects emotional reactions. In left-handers, the right temporal lobe is responsible for speech, and the left – for emotions. The frontal lobe controls movements and balance, as well as is connected with the emotional and mental sphere and personal characteristics of the character. The parietal lobe analyzes impulses from the organs of touch.

Brain

Posted on June 7, 2019  in Medical news

This, of course, the most important organ of the nervous system. It is covered with a hard shell (mening) and floats inside the skull in the so-called cerebrospinal fluid. Although the human brain weighs less than two kilograms on average, it is an exceptionally complex organ.
The brain contains many billions of neurons. Due to the complex interweaving of axons, each neuron is connected to several thousand others. The complexity of these interweaving is so great that sometimes it goes beyond our understanding. Despite this, studies of the most complex organ in the human body are conducted and bear fruit. A fruitful approach to the study of the brain is to examine it in parts and find out the specific functions of each of them.
The main parts of the brain are the hindbrain, midbrain and forebrain. Figure 3-5 shows their location relative to each other. If we go upwards from the spinal cord, then the hind brain will be the first on our way.

Posterior brain

The main components of the hindbrain are the medulla, the pons, and the cerebellum. The medulla is located at the junction of the brain with the spinal cord and is essentially a continuation of the spinal cord. It regulates such extremely important functions of the body as breathing, heartbeat, blood pressure, digestion, swallowing and vomiting. Disruption of the medulla oblongata is very dangerous, and taking drugs that are inactive on the medulla, a person questions his life. When the content of toxic substances in the medulla oblongata rises dramatically, the emetic center is activated to cleanse the body. Therefore, when very drunk people often feel sick. Further in the back brain the bridge is located. It provides training for the transmission of impulses through the spinal cord, and is also partly responsible for sleep and wakefulness.A special path of impulses (not shown in Figure 3-5), known as the reticular formation, passes through the medulla oblongata and the bridge. It is very important for alertness and wakefulness. Obviously, substances that cause sleep (barbiturates and tranquilizers) act on this part of the brain.
The third major part of the hindbrain is the cerebellum. It has a very complex structure, consists of several billion neurons. Its main task is to regulate the movement of body parts. The mechanism of action of the cerebellum is practically incomprehensible to us, it is only known that it coordinates the most diverse gestures, speech and maintains balance. Drugs that cause inconsistency in movements and loss of balance (for example, alcohol) affect the cerebellum.

The midbrain

It consists of two small formations: the internal mounds and external mounds. Internal hillocks are parts of the hearing system, they localize the sound source in space. Outer mounds do the same with visual stimuli. Localization of objects and sending messages about them are the main functions of these parts of the brain. Recognition and interpretation of visual and auditory stimuli occur somewhere in another part of the brain.

Other neurotransmitters

Posted on June 3, 2019  in Pain

For a long time, four of the above neurotransmitters were considered the only main substances acting in the process of transmitting nerve impulses. But with the development of more sophisticated research technologies, it became clear that we are still waiting for the discovery of many more neurotransmitters.
In the late seventies, substances similar in chemical properties to opiates were found in the mammalian brain tissue. Because of this similarity, they were called endorphins (short for “endogenous morphine”). Their functions in the body are varied and are not yet completely clear, but no doubt that these substances contribute to the relief of pain. For a detailed description of endorphins, see Chapter 9.
Another important neurotransmitter is gamma-aminobutyric acid (GABA). Its brain tissue contains much more than other known neurotransmitters, and it acts a little differently. The analogy of the key and the lock still works, but GABA, entering the receptor, does not open, but closes the lock, that is, it does not excite a neuron, but on the contrary, prevents it. Therefore, it is usually called the suppressive neurotransmitter (although other neurotransmitters can act in certain synapses in this capacity). If the GABAergic receptor of the neuron is activated, then in order for the neuron to be excited, a very large number of appropriate neurotransmitters are needed. A lot of drugs are now known to act like GABA. These are classic depressants: barbiturates, diazepam (Valium) and chlordiazepoxide (Librium) tranquilizers, and alcohol.

Nervous system

After considering the smallest parts of the nervous system and the effects of drugs at the neuron level, consider the entire nervous system as a whole. Its structure is depicted in Figure 3-3. It has two fundamentally different departments: the central nervous system and the peripheral nervous system. The central nervous system includes the brain and spinal cord. All nerve tissues outside of them belong to the peripheral nervous system. It consists of nerves (axonal ligaments) that transmit information from the sense organs to the brain (sensory nerves) and from the brain to muscles (motor nerves).

Vegetative nervous system 

In addition to the nerve endings, the peripheral nervous system has an important regulatory system, called the autonomic nervous system. It regulates automatic reactions, and in turn is divided into two parts. The sympathetic branch of the autonomic nervous system is activated during the period of emotional recovery by the release of adrenaline and norepinephrine from the special glands. She is responsible for various physiological changes that accompany instantaneous subconscious reactions: an increase in pressure, increased heart rate and respiration, dilated pupils, perspiration, dry mouth, changes in blood flow in the body (it pours from the internal organs and rushes to the brain and large muscles). Many psychoactive substances cause the same changes in the body. Such substances are called sympathomimetics, and they include cocaine,amphetamines and some LSD-type hallucinogens. Other substances block a certain type of sympathetic norepinephrine receptors, the so-called beta receptors. They regulate blood pressure. Substances called beta-blockers (which include propranolol) are widely used in the treatment of hypertension.
The second, parasympathetic branch of the autonomic nervous system is associated with actions opposite to those of the sympathetic. It reduces pulse, blood pressure, etc. Unlike sympathetic neurons, the synapses of the neurons of this system are mostly cholinergic. Substances that act directly on the parasympathetic nervous system are usually very toxic. For example, the nervous paralytic gases zorin and soman bind acetylcholinesterase, which leads to excessive activity of this branch of the nervous system. The result is death from suffocation or cardiac arrest.

Monoamines

Three important neurotransmitters belonging to the same amino group are called monoamines, norepinephrine (norepinephrine), dopamine and serotonin. Like acetylcholine, norepinephrine was discovered long ago, because it is also located outside the brain. This is the main chemical that regulates the physical changes that accompany emotional recovery. It is also found in the brain and plays the role of a neurotransmitter responsible for the feeling of hunger, wakefulness and waking up from sleep. Serotonin is found in all parts of the brain and plays an important role in regulating sleep. Dopamine is the main neurotransmitter in areas of the brain that provide consistent movements of body parts. This discovery gave rise to the hypothesis that dopamine deficiency can be the main cause of Parkinson’s disease, which affects mainly older people and is characterized by progressive movement inconsistency, hardening of muscles and trembling in the body. In accordance with this hypothesis, new approaches to the treatment of

Parkinson’s disease began to be applied, including the use of the drug L-DOPA, the “initial substance” of dopamine. L-DOPA was prescribed to patients to restore the level of dopamine in the tissues, and gave amazing results. Acceptance of dopamine itself is ineffective, since it cannot get into the brain along with blood. The brain is protected from toxic substances by the blood filtration system or the blood barrier of the brain (encephalogen barrier), which also detains dopamine. But L-Dofa overcomes this barrier and, getting into the brain, turns into dopamine. The use of L-Dov in the treatment of Parkinson’s disease is a vivid example of the value of scientific studies of neurotransmitters. Although L-Dova does not eliminate the disease at all (the loss of dopaminergic neurons continues, and even this drug cannot completely fill it), it prolongs the life of people with Parkinson’s disease, who would have died many years earlier without it.

In addition to these functions, monoamines are closely related to mood and emotional disorders. The discovery of substances affecting monoamines has revolutionized psychiatry. There is strong evidence that severe clinical cases of depression are associated with biological disorders. According to the latest theories, clinical depression occurs due to changes in the level of monoamines, especially norepinephrine and serotonin. This is also confirmed by the fact that drugs destroying monoamines cause depression. As we have said, reserpine causes leakage in the vesicles of nerve endings and the subsequent destruction of neurotransmitters, as a result of which there is a shortage of monoamines in the body. Drugs used in the treatment of depression significantly increase the production of norepinephrine and serotonin.

Monoamines, and especially dopamine, also constitute the biochemical basis for the occurrence of another serious mental illness, schizophrenia. When it happens, there is an almost complete loss of connection with reality, manifested in deceptions of feelings, hallucinations, disturbed emotional reactions and falling out of public relations. It is proved that these symptoms are caused by increased activity of monoamines. First, all drugs used to treat schizophrenia block monoamines. There is a very close relationship between the strength of the therapeutic effect of the drug and its ability to block dopamine receptors. In addition, compounds incapable of this, as a rule, do not relieve the symptoms of schizophrenia, even if they possess all the other properties inherent in effective drugs. Another interesting piece of evidence: stimulant drugs such as cocaine and amphetamines increase dopaminergic brain activity. Although small or moderate doses of these stimulants improve mood, overdosing often leads to paranoid disorders and loss of connection with reality, which almost exactly repeats the symptoms of schizophrenia. When the effect of the drug diminishes and dopaminergic activity returns to normal, these symptoms disappear. This again indicates a connection between increased dopaminergic activity and schizophrenia.