Dependence of the effect of drugs on the dose. Dependence of the action of drugs on their properties

In experimental pharmacology, an alternative or graduated system is used to establish the dose. In an alternative system, the number of animals in which drugs produce a pharmacological effect is determined as a percentage. In a graduated system, the degree of change in effect depending on the dose is recorded. Thus, for an alternative system, an effective dose of ED 50 indicates a dose that produces an effect in 50% of animals; in a graded system, it is a dose that provides a pharmacological response equal to 50% of the maximum possible.

All drugs have therapeutic, toxic and lethal (lethal) doses.

Therapeutic doses:

· minimum (threshold) therapeutic dose - the minimum amount of a drug that causes a therapeutic effect;

· average therapeutic dose - the range of doses in which the drug has an optimal preventive or therapeutic effect in the majority of patients;

· maximum therapeutic dose- the maximum amount of the drug that does not have a toxic effect.

Toxic doses:

· minimum toxic dose - a dose that causes mild symptoms of intoxication or poisoning in 10% of cases;

· average toxic dose - dose causing moderate intoxication or poisoning in 50% of cases;

· maximum toxic dose - a dose that causes severe intoxication or intoxication in 100% of cases, but does not cause death.

Lethal doses:

· minimum lethal dose(DL 10) - dose causing death in 10% of observations;

· mean lethal dose(DL 50) - dose that causes death in 50% of observations;

· maximum lethal dose(DL 100) - a dose that causes the death of all poisoned animals.

In an experiment, therapeutic, toxic and lethal doses are calculated using mathematical calculations. Lists A and B drugs have higher single and daily doses.

Breadth of therapeutic action- the range between the average and maximum therapeutic doses. Therapeutic index- the ratio of the effective dose ED 50 to the lethal dose DL 50.

To achieve a rapid therapeutic effect, drugs are sometimes prescribed in loading doses (antibiotics, sulfonamides). Drugs capable of accumulation are used in maintenance doses. In pediatric practice, medications are dosed based on the weight or surface area of the child's body.

The dependence of the effect of drugs on the dose can be not only quantitative, but also qualitative. Acetylcholine in small doses excites M-cholinergic receptors; in doses 10 times greater - also H-cholinergic receptors. Sodium hydroxybutyrate in small doses has an analgesic and sedative effect, in medium doses it has an anticonvulsant and hypnotic effect, and in large doses it has an anesthetic effect.

Effect of the drug depends on its quantity entering the body, i.e., on the dose. If the prescribed dose is below the threshold (subthreshold), there is no effect. Depending on the nature of the effect, increasing the dose may lead to its intensification. Thus, the effect of antipyretic or antihypertensive drugs can be quantitatively expressed using a graph, which indicates, respectively, the degree of decrease in body temperature or.

Dependency Variations effect of drug on dose due to the sensitivity of the particular person taking the drug; Different patients require different doses to achieve the same effect. Differences in sensitivity are particularly evident in all-or-none phenomena.

As an illustration, we present experiment, in which subjects react according to the “all or nothing” principle - Straub's test. In response to morphine administration, mice develop agitation, which manifests itself as abnormal tail and limb positioning. The dose dependence of this phenomenon is observed in groups of animals (10 mice per group) that are administered increasing doses of morphine.

At low dose administration Only the most sensitive individuals react; as the dose increases, the number of responders increases, and at the maximum dose, the effect develops in all animals in the group. There is a relationship between the number of responding individuals and the dose administered. At a dose of 2 mg/kg, 1 in 10 animals responds; at a dose of 10 mg/kg - 5 out of 10 animals. This dependence of the frequency of the development of the effect and the dose is the result of different sensitivity of individuals, which, as a rule, is characterized by a lognormal distribution.

If cumulative frequency(the total number of animals that develop a response to a particular dose) is marked on the logarithm of the dose (x-axis), an S-shaped curve appears. The lower point of the curve corresponds to the dose to which half of the animals in the group respond. The dose range, covering the dose-response relationship and frequency of effect, reflects variations in individual sensitivity to the drug. The graph of dose versus frequency of effect is similar in shape to the graph of effect versus dose, but there are some differences. Dose dependence can be assessed in one person, i.e. it represents the dependence of the effect on the concentration of the drug in the blood.

Grade dose-dependent effect in the group is difficult due to different sensitivity in individual patients. To assess biological variation, measurements are taken in representative groups and the results are averaged. Thus, the recommended therapeutic doses appear to be adequate for most patients, but not always for a particular individual.

At the core variations sensitivity lies in differences in pharmacokinetics (same dose - different concentration in the blood) or different sensitivity of the target organ (same concentration in the blood - different effect).

To enhance therapeutic safety Clinical pharmacologists are trying to figure out what causes differences in sensitivity between patients. This area of pharmacology is called pharmacogenetics. Often the cause is a difference in the properties or activity of enzymes. In addition, ethnic variability in sensitivity has been observed. Knowing this, the doctor should try to find out the patient's metabolic status before prescribing a particular drug.

The monograph substantiates the position that there are not only treatment methods based on the effect of drugs, but also treatment principles that use the body's response to these effects.

V.V. Korpachev, Doctor of Medical Sciences, Professor, Head of the Department of Pharmacotherapy of Endocrine Diseases, Institute of Endocrinology and Metabolism named after. V.P. Komissarenko AMS of Ukraine

This material is one of the chapters of the book “Fundamental principles of homeopathic pharmacotherapy” (Kyiv, “Chetverta Khvilya”, 2005), the author of which is Doctor of Medical Sciences, Professor Vadim Valerievich Korpachev.

Various fundamental approaches to treatment can significantly expand the capabilities of medicine and make it possible to achieve success where the use of drugs based on generally accepted treatment principles will not be effective enough. The book is intended for doctors, clinical pharmacologists, pharmacists and specialists who are interested in philosophical problems of medicine and pharmacotherapy.

The patterns of manifestation of medicinal properties depending on the dose, as well as on the phase of action, are one of the most important issues in pharmacology, pharmacotherapy, and possibly all of medicine. Knowledge of these patterns can significantly expand the possibilities of treating many diseases, making it more targeted and physiological. The dependence of the strength of a drug on its dose has always attracted the attention of doctors. Even Ibn Sina in the second book of the “Canon” wrote: “If ten people carry a load over a distance of one fars in one day, it does not follow that five people can carry it over any distance, much less over a distance of half-farsakh. It also does not follow from this that half of this burden can be separated so that these five, having received it separately, can carry it... Therefore, not every time the mass of the medicine decreases and its strength decreases, you see that its effect is greater. becomes smaller the same number of times. It is also not at all necessary that the medicine itself should have an effect corresponding to its small magnitude on something that is susceptible to the influence of a large amount of the medicine.”

At the dawn of the development of medicine, it was found that as the dose increases, the strength of the medicine also increases. Now this is known not only to pharmacologists, but also to every clinician. But to what extent does this increase occur? And is there any regularity at all, that is, is an increase in the dose in certain respects accompanied by the same correct increase in the strength of its action, or is everything different?

After conducting a series of studies on the red blood cells of aquarium fish with certain drugs, researcher Jacouffe, back in the last century, derived a law that stated that the increase in the strength of the poison is not proportional to the increase in dose - it goes much faster than the latter. He found that with a doubling of the dose, the strength of action increases not twice, but by 11, 14, 15, 30, 50 times. But when in the laboratory of N.P. Kravkova, his employee A.M. Lagovsky conducted research on an isolated heart with alkaloids, this was not confirmed. In his dissertation for the degree of Doctor of Medicine, “On the dependence of the potency of poisons on the dose,” defended in 1911, he demonstrated that in most cases the potency of the test substance is proportional to its dose.

And yet, later researchers confirmed Jacuff’s findings. It was found that the disproportionality is more pronounced at low doses than at large ones.

It has been empirically established that each drug has a minimum dose, below which it is no longer effective. This minimum dose varies from product to drug. As the dose increases, a simple increase in effect occurs, or toxic effects alternately occur in different organs. For therapeutic purposes, the first action is usually used. There are three types of doses: small, medium and large. Therapeutic doses are followed by toxic and fatal ones, which threaten life or even interrupt it. For many substances, the toxic and lethal doses are much higher than the therapeutic ones, but for some they differ from the latter very slightly. In order to prevent poisoning, therapeutic guidelines and textbooks on pharmacology indicate the highest single and daily doses. The saying of Paracelsus “Everything is poison, and nothing is without poison; just one dose makes the poison invisible” was confirmed in practice. Many poisons have found use in modern medicine when used in non-toxic doses. An example is the poisons of bees and snakes. Even chemical warfare agents can be used for medicinal purposes. The chemical warfare agent mustard gas (dichlorodiethyl sulfide) is known, the toxic properties of which were experienced by the famous chemist N. Zelinsky, who was one of the first to synthesize it. Today, nitrogen mustards are highly effective antitumor drugs.

The pharmacological response varies differently depending on the properties of the drug substance (Fig. 1). If it enhances function in small doses, increasing the dose may cause a reverse effect, which will be a manifestation of its toxic properties. When a pharmacological drug reduces function in low doses, increasing the dose deepens this effect to the point of toxicity.

In 1887, the first part of this pattern was formulated as the Arndt-Schultz rule, according to which “small doses of medicinal substances excite, medium doses enhance, large doses inhibit, and very large doses paralyze the activity of living elements.” This rule does not apply to all medicinal substances. The range of all doses for the same drug is also quite wide. Therefore, many researchers most often studied the patterns of the dose-response indicator in a certain range of doses, most often in the field of therapeutic or toxic.

Three patterns can be distinguished:

the strength of action increases in proportion to the increase in dose, for example, with fatty anesthetics (chloroform, ether, alcohols);
an increase in pharmacological activity is observed with a slight increase in the initial threshold concentrations, and a further increase in dose causes only a slight increase in the effect (this pattern, for example, is exhibited by morphine, pilocarpine and histamine);
As the dose increases, the pharmacological effect initially increases slightly and then becomes stronger.

These patterns are depicted in Figure 2. As can be seen from the curves shown there, the pharmacological response does not always increase in proportion to the dose. In some cases, the effect increases to a greater or lesser extent. The S-shaped curve is most common in studies of toxic and lethal doses, but is rare in the therapeutic dose range. It should be noted that the curves shown in Figure 2 are part of the graph shown in Figure 1.

Soviet pharmacologist A.N. Kudrin proved the existence of a step-like dependence of the pharmacological effect on the dose, when the transition from one reaction value to another sometimes occurs abruptly, and sometimes gradually. This pattern is typical for therapeutic doses.

The effects caused by the administration of toxic doses depend not only on the size of the dose itself or the concentration of the substance, but also on the time of its exposure. Based on the analysis of various relationships between concentration and time, all poisons were divided into two groups: chronoconcentration and concentration. The effect of the latter depends on their concentration and is not determined by the time of action (these are volatile drugs and local anesthetics - cocaine, curare). The toxic effect of chronoconcentration poisons significantly depends on the time of their action. These include substances that affect metabolism and some enzyme systems.

Based on experimental data, it was possible to significantly expand the range of doses used.

There are these types of doses:

subthreshold – does not cause a physiological effect according to the selected indicator;
threshold – causing initial manifestations of physiological action according to the recorded indicator;
therapeutic – the range of doses that cause a therapeutic effect in experimental therapy;
toxic – causing poisoning (severe disruption of the functions and structure of the body);
maximum tolerated (tolerant) (DMT) – causing poisoning without fatalities;
effective (ED) – causing a programmable effect in a certain (specified) percentage of cases;
LD50 – causing death in 50% of experimental animals;
LD100 – causing death in 100% of experimental animals.

It is known that the same substances may have no effect on a healthy organism or organ and, on the contrary, exhibit a pronounced physiological effect in relation to the patient. For example, a healthy heart does not react as much to digitalis as a diseased one. Small doses of some hormonal substances have a pronounced effect on a sick body, without showing activity on a healthy one.

This phenomenon can probably be explained based on the teachings of N.E. Vvedensky: under the influence of various external stimuli, a state occurs when biological objects respond to a small stimulus with an increased reaction (paradoxical phase). A similar pattern was observed not only under the action of physical factors, but also with many medicinal substances. The paradoxical phase is also characterized by a significant decrease in the ability to respond to stronger influences. In the mechanism of action of drugs, this phenomenon is also likely to have important practical significance.

At the end of the last century, German pharmacologists G. Nothnagel and M. Rossbach wrote in their “Guide to Pharmacology” (1885) that in a curarized state, in some stages of poisoning, with the slightest touch of the skin, for example, by lightly running a finger over it, by blowing on it mouth, there was a prolonged increase in blood pressure; but the strongest painful interventions in the same places (cauterization with mustard alcohol, concentrated acids, hot iron, etc.) did not have the slightest effect on blood pressure - moreover, occasionally even a decrease in pressure was observed. They also noted that in healthy, unpoisoned animals, neither mild tactile stimulation of the skin nor even the most severe painful interventions affected blood pressure; neither electrical, nor chemical or “caustic” stimulation produced the expected effects.

So, increasing the dose of a drug enhances its pharmacological effect in the range of both therapeutic and toxic doses. If a drug stimulates function, then in the range of toxic doses the opposite effect is observed - inhibition. Against the background of altered reactivity of the body, perverted reactions to the administration of small and large doses of medicinal substances may be observed.

But not only the dose size determines the pharmacological effect. It turned out that the drug exhibits an ambiguous effect - inhibition of function or enhancement of it, it causes a pharmacological reaction, which over time consists of several phases. The concept of the phases of action of drugs was formulated at the beginning of the century, when the effect of muscarine on the isolated heart was studied. After immersing the heart in a muscarine solution, it first stopped in the relaxation phase (diastole), and then began to contract again. After washing in a pure nutrient medium (when the tissue was washed away from the poison), a secondary weakening of cardiac activity was noted. The researchers concluded that the moment the poison is released is also a pharmacologically active phase.

Subsequently, it was proven that a similar reaction is also observed when exposed to other substances (pilocarpine, arecoline, adrenaline) and other isolated organs.

In 1911 N.P. Kravkov wrote that just as when studying the effect of electric current on a nerve one has to take into account the moment of its closing and opening, so when studying the effect of poison it is necessary to take into account not only the moment of its entry into the tissues and their saturation, but also the exit from them . In the laboratory of N.P. Kravkova later found that the substance under study does not always give the same effect in the “entry phase” and in the “exit phase.” For example, veratrine and strychnine constrict the vessels of the isolated rabbit ear in the “entry phase” and dilate in the “exit phase.” Alcohol constricts blood vessels in the “entry phase” and dilates them in the “exit phase.” With unambiguous action in both phases, the effect in the “exit phase” was often significantly higher. In one of his works, Kravkov wrote that when studying the effect of any poison, one should distinguish between the phase of its entry into tissues, the phase of saturation of tissues (or stay in them) and, finally, the phase of exit from them. Note that these results were obtained on isolated organs and, therefore, cannot be completely transferred to the whole organism. At present, it is difficult to answer whether such patterns will appear, for example, when the body is saturated with any pharmacological drug. Kravkov's hypothesis has only historical significance.

To be continued in the next issues.

Drugs can affect the body differently depending on its functional state. As a rule, stimulant-type substances exert their effect more strongly when they inhibit the functions of the organ on which they act, and, conversely, inhibitory substances act more strongly against the background of excitement.

The effect of drugs may vary depending on pathological condition body. Some pharmacological substances exhibit their effects only under pathological conditions. Thus, antipyretic substances (for example, acetylsalicylic acid) lower body temperature only if it increases; Cardiac glycosides clearly stimulate cardiac activity only in heart failure.

Pathological conditions of the body can change the effect of drugs: enhance (for example, the effect of barbiturates in liver diseases) or, conversely, weaken (for example, local anesthetic substances in conditions of tissue inflammation reduce their activity).

12. The concept of dose and concentration. Types, expressions and dose designations. Dependence of drug action on dose and concentration. The breadth of therapeutic action of medicinal substances, its significance.

Drug dose is the amount of medication required to provide a therapeutic, prophylactic or diagnostic effect.

Types of doses - therapeutic, prophylactic, diagnostic; minimum, average, maximum; one-time, daily, course; toxic and lethal (in case of drug poisoning).

Drug concentration is the amount of drug per unit volume.

Expression and designation of doses.

The units for measuring drug doses are:

1 gram (if the medicine is dosed by weight);
1 ml (if dosed by volume);
Measurement in drops
ED (if the activity of the drug is established on biological objects)

Dependence of drug action on dose and concentration.

It has been empirically established that each drug has a minimum dose, below which it is no longer effective. This minimum dose varies from product to drug. As the dose increases, a simple increase in effect occurs, or toxic effects alternately occur in different organs. The pharmacological response varies differently depending on the properties of the drug. If it increases function in small doses, increasing the dose may cause the opposite effect, which will be a manifestation of its toxic properties. When a pharmacological drug reduces function in low doses, increasing the dose deepens this effect to the point of toxicity. The effects caused by the administration of toxic doses depend not only on the size of the dose itself or the concentration of the substance, but also on the time of its exposure . Based on the analysis of various relationships between concentration and time, all poisons were divided into two groups: chronoconcentration and concentration. The effect of the latter depends on their concentration and is not determined by the time of action (these are volatile drugs and local anesthetics - cocaine, curare). The toxic effect of chronoconcentration poisons significantly depends on the time of their action. These include substances that affect metabolism and some enzyme systems. Under the influence of various external stimuli, a state occurs when biological objects respond to a small stimulus with an increased reaction (paradoxical phase). increasing the dose of a drug enhances its pharmacological effect in the range of both therapeutic and toxic doses. If a drug stimulates function, then in the range of toxic doses the opposite effect is observed - inhibition. Against the background of altered reactivity of the body, perverted reactions to the administration of small and large doses of medicinal substances may be observed.

The breadth of therapeutic action is the range of doses of a drug from the minimum effective to the minimum toxic dose. This interval can also be considered as the range of acceptable levels of a substance in plasma in which a therapeutic effect is observed. The minimum level of a substance in plasma that provides the required effect is the lower limit of the therapeutic range, and its maximum limit is the level at which toxic effects occur.

13. The concept of pharmacodynamics, pharmacokinetics, pharmacogenetics. Types of action of medicinal substances: local, reflex,

14. resorptive, main and secondary, direct and indirect (mediated), reversible and irreversible, selective (elective), etiotropic.

Pharmacodynamics – changes in the functions of cells, organs, and tissues of the body in response to the administration of a drug. It examines the mechanism, nature and type of action of the drug.

Pharmacokinetics – a set of processes leading to the creation in an organism, tissue, organ, cell, of a drug concentration sufficient to form a complex with a biosubstrate. (Absorption, distribution, transformation, and release of a drug)

Pharmacogenetics - a section of medical genetics and pharmacology that studies the nature of the body’s reactions to drugs depending on hereditary factors.

Local action of the drug. things - the action of a thing that occurs at the place of its application. For example, enveloping materials cover the mucous membrane, preventing irritation of the endings of afferent nerves. With superficial anesthesia, application of an anesthetic to the mucous membrane leads to a block of sensory nerve endings only at the site of application of the drug.

Reflex – substances affect extero- or interoceptors and the effect is manifested by a change in the state of either the corresponding nerve centers or executive organs. (The use of mustard plasters for pathologies of the respiratory organs reflexively improves their trophism)

Resorptive – the action of a substance that develops after its absorption, entry into the general bloodstream and then into the tissues. Depends on the route of administration. Weds and their ability to penetrate biological barriers.

Main action(main) - the effect of the medicine that is expected when using it in this particular case

All other effects are called side effects. Not all side effects are unwanted. For example, diphenhydramine can be used by patients as a sleeping pill, because side effect - depression of the central nervous system, drowsiness.

Direct action - is implemented at the site of direct contact of the substance with the tissue. Its consequence is indirect effects. For example, cardiac glycosides have a direct cardiac stimulating effect. At the same time, they improve hemodynamics in patients with heart failure, reduce congestion in tissues, increase diuresis, etc. These are indirect effects.

Reversible action- disappears after a certain time, which is explained by the dissociation of the drug-substrate complex.

Irreversible action - if such a complex does not dissociate, i.e. It is based on a covalent bond.

Selective action - the substance interacts only with functionally unambiguous receptors of a certain location and does not affect other receptors. It is based on complementarity between the structural organization of the substance and the receptor.

15. Mechanisms of action of drugs: chemical, physical, cytoreceptor, effect on ion channels and biologically active substances, competitive, enzymatic, etc. The concept of agonists and antagonists, agonists-antagonists.

To reproduce the pharmacological effect, the drug must interact with the molecules of the body's cells. The connection of drugs with a biological substrate-ligand can be achieved through chemical, physical, physicochemical interaction.

Special cellular structures that ensure interaction between a drug and the body are called receptors.

Receptors are functionally active macromolecules or their fragments (mainly protein molecules - lipoproteins, glycoproteins, nucleoproteins), which are targets for endogenous ligands (mediators, hormones, other biologically active substances). Receptors that interact with certain drugs are called specific.

Receptors can be located in the cell membrane (membrane receptors), inside the cell - in the cytoplasm or in the nucleus (intracellular receptors). There are 4 known types of receptors, 3 of which are membrane receptors:

receptors directly coupled to enzymes;

receptors directly coupled to ion channels;

receptors that interact with G proteins;

receptors that regulate DNA transcription.

When drug compounds interact with a receptor, numerous effects occur, with biochemical and physiological changes occurring in many organs and systems, which can be represented as typical mechanisms of interaction between drugs and receptors.

The interaction between the substance and the receptor is carried out due to the formation of intermolecular bonds of various types: hydrogen, van der Waals, ionic, less often covalent, which are especially strong. Medicines bound by this type exhibit irreversible effects. An example is acetylsalicylic acid, which irreversibly inhibits platelet cyclooxygenase, which makes it highly effective as an antiplatelet agent, but at the same time it becomes more dangerous regarding the development of gastric bleeding. Other types of intermolecular bonds disintegrate after a certain time, which determines the reversible effect of most drugs.

The drug, having a structure close to the metabolite (mediator), interacts with the receptor, causing its stimulation (simulating the action of the mediator). The drug is called an agonist. The ability of a drug to bind to certain receptors is determined by their structure and is designated by the term “affinity”. The quantitative measure of affinity is the dissociation constant (K0).

A drug that is similar in structure to the metabolite but prevents it from binding to the receptor is called an antagonist. If an antagonist drug binds to the same receptors as endogenous ligands, they are called competitive antagonists; if they bind to other sites on macromolecules that are functionally associated with the receptor, they are called non-competitive antagonists. Medicines (by acting on receptors) can combine the properties of agonists and antagonists. In this case, they are called agonist-antagonists, or synergistic antagonists. An example is the narcotic analgesic pentazoiin, which acts as a δ-agonist and κ-opioid receptors and an antagonist of μ-receptors. If a substance affects only a specific receptor subtype, it exhibits a selective effect. In particular, the antihypertensive drug prazosin selectively blocks α1-adrenergic receptors, in contrast to the α1 and α2-adrenergic blocker phentolamine.

When interacting with the allosteric center of the receptor, drugs cause conformational changes in the structure of the receptor, including activity towards body metabolites - a modulating effect (tranquilizers, benzodiazepine derivatives). The effect of the drug can be realized due to the release of metabolites from bonds with protein or other substrates.

Some drugs increase or inhibit the activity of specific enzymes. For example, galantamine and proserine reduce the activity of cholinesterase, which destroys acetylcholine, and cause effects characteristic of excitation of the parasympathetic nervous system. Monoamine oxidase inhibitors (pyrasidol, nialamide), which prevent the destruction of adrenaline, increase the activity of the sympathetic nervous system. Phenobarbital and ziscorine, by increasing the activity of liver glucoronyltransferase, reduce the level of bilirubin in the blood. Medicines can inhibit the activity of folic acid reductase, kinases, angiotensin-converting enzyme, plasmin, kalikriin, nitric oxide synthetase, etc. and thereby change the biochemical processes dependent on them.

A number of medicinal substances exhibit a physical and chemical effect on cell membranes. The activity of cells of the nervous and muscular systems depends on ion flows that determine the transmembrane electrical potential. Some drugs alter ion transport. This is how antiarrhythmic, anticonvulsant drugs, general anesthesia, and local anesthetics work. A number of drugs from the group of calcium channel blockers (calcium antagonists) are widely used to treat arterial hypertension, coronary heart disease (nifedipine, amlodipine) and cardiac arrhythmias (diltiazem, verapamil).

Blockers of voltage-gated K+ channels - amiodarone, ornid, sotalol - have an effective antiarrhythmic effect. Sulfonylurea derivatives - glibenclamide (manninil), glimepiride samaril block ATP-dependent K+ channels, and therefore stimulate insulin secretion by pancreatic β-cells and are used to treat diabetes mellitus.

Drugs can directly interact with small molecules or ions inside cells and cause direct chemical interactions. For example, ethylenediaminetetraacetic acid (EDTA) strongly binds lead and other heavy metal ions. The principle of direct chemical interaction underlies the use of many antidotes for poisoning by chemical substances. Another example is the neutralization of hydrochloric acid with antacids. Physico-chemical interaction is observed between heparin and its antagonist protamine sulfate, which is based on the difference in the charges of their molecules (negative for heparin and positive for protamine sulfate).

Some drugs are able to be involved in metabolic processes in the body due to the proximity of their structure to the structure of natural metabolites. This effect is exerted by sulfonamide drugs, which are structural analogues of para-aminobenzoic acid. This is the basis for the mechanism of action of some drugs that are used to treat cancer (methotrexate, mercaptopurine, which, respectively, are antagonists of folic acid and purine). The mechanism of action of drugs may be based on nonspecific changes due to their physical or chemical properties. In particular, the diuretic effect of mannitol is due to its ability to increase osmotic pressure in the renal tubules.

16. Types of drug therapy (symptomatic, pathogenetic, replacement, etiotropic, preventive).

Prophylactic use refers to the prevention of certain diseases. For this purpose, disinfectants, chemotherapeutic substances and other desirable symptoms are used

Causative therapy – aimed at eliminating the cause of the disease (antibiotics act on bacteria)

Symptomatic therapy is the elimination of unwanted symptoms (for example, pain), which has a significant impact on the course of the main pathological process. In this regard, and in many cases, symptomatic therapy plays the role of pathogenetic therapy.

Replacement therapy – used for deficiency of natural nutrients. So, with insufficiency of the endocrine glands

17-20 absent

21. Carcinogenic effect. Idiosyncrasy, its differences from allergic reactions, manifestations in dentistry, measures to help and prevention.

Carcinogenicity is the ability of substances to cause the development of malignant tumors. Derivatives of benzene, phenol, tar ointments, and cauterizing agents have a carcinogenic effect. Sex hormones and other stimulators of protein synthesis can promote the growth and metastasis of tumors. Idiosyncrasy can be one of the causes of adverse reactions to substances. Idiosyncrasy is a painful reaction that occurs in some people in response to certain nonspecific (as opposed to allergies) irritants. Idiosyncrasy is based on innate increased reactivity and sensitivity to certain stimuli or a reaction that occurs in the body as a result of repeated weak exposure to certain substances and is not accompanied by the production of antibodies. Idiosyncrasy differs from allergies in that it can develop even after the first contact with a substance. Soon after contact with the irritant, a headache appears, the temperature rises, sometimes mental agitation, disorders of the digestive system (nausea, vomiting, diarrhea), breathing (shortness of breath, runny nose, etc.), swelling of the skin and mucous membranes, and urticaria occur. These phenomena, caused by circulatory disorders, increased vascular permeability, and smooth muscle spasms, usually disappear soon, but sometimes last for several days. The transferred reaction does not create insensitivity to repeated action of the agent.

22. Features of the action of drugs with repeated and prolonged administration: drug dependence, sensitization, addiction, tachyphylaxis, cumulation.

With repeated use of medicinal substances, their effect may change either in the direction of increasing the effect or decreasing it. The increase in the effect of a number of substances is associated with their ability to cumulation. Cumulation can be material and functional. Material cumulation-accumulation of a pharmacological substance in the body. This is typical for long-acting drugs that are slowly released or persistently bind in the body (cardiac glycosides, digitalis). Functional cumulation– in which the effect, not the substance, accumulates (with alcoholism, increasing changes in the functions of the central nervous system lead to the development of delirium tremens. Ethyl alcohol quickly oxidizes and does not linger in the tissues. Only its neurotropic effects are cumulative).

Habituation is a decrease in the effectiveness of substances upon repeated use. It can occur with a decrease in the absorption of the substance, an increase in the rate of its inactivation and an increase in the intensity of its administration. It is possible that addiction to a number of substances is due to a decrease in the sensitivity of receptor formations to them or a decrease in their density in tissues. In case of addiction, to obtain the initial effect, the dose of the drug must be increased or one substance replaced with another.

Tachyphylaxis- a special type of addiction. Addiction develops very quickly, sometimes after the first administration of the substance.

Drug addiction- develops to certain substances upon repeated administration. It is manifested by an irresistible desire to take a substance, usually with the aim of increasing mood, improving well-being, eliminating unpleasant sensations and experiences, including those that arose during the withdrawal of substances that cause drug dependence. Distinguish mental And physical drug addiction. When mental drug dependence stopping the drug only causes emotional discomfort. When taking certain substances (heroin, morphine). This is a more pronounced degree of dependence. Withdrawal of the drug in this case causes a serious condition, which, in addition to sudden mental changes, is manifested by various and often serious somatic disorders associated with disorders of the functions of many body systems, including death.

23. Drug allergies. Differences between allergic and toxic effects of drugs. Features of allergies in dental patients, ways of prevention and treatment.

Drug allergies are independent of the dose of the substance administered. Medicines act as antigens. There are 4 types of drug allergies.

Type 1. Immediate allergy. This type of hypersensitivity is associated with the involvement of an IgE antibody reaction. This manifests itself as urticaria, vascular edema, rhinitis, bronchospasm, and anaphylactic shock. Such reactions are possible when using penicillins and sulfonamides.

Type 2. In this type of drug allergy, IgG-IgM antibodies, activating the complement system, interact with circulating blood cells and cause their lysis. (for example, methyldopa can cause hemolytic anemia, quinidine - thrombocytopenic purpura.

Type 3. IgG, IgM, IgE antibodies take part in the development of this type. The Antigen-Antibody-compliment complex interacts with the vascular endothelium and damages it. Serum sickness occurs, manifested by urticaria, arthralgia, arthritis, lymphadenopathy, and fever. May cause: penicillins, sulfonamides, iodides.

Type 4. In this case, the reaction is mediated through cellular immune mechanisms, including sensitized T-lymphocytes and macrophages. It occurs when the substance is applied locally and manifests itself as contact dermatitis.

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