Reduced effectiveness of medicinal substances with repeated use. A. Repeated use of medicinal substances. A measure of the activity of a drug substance is

With repeated administration of medicinal substances, phenomena of habituation, drug dependence (addiction), cumulation, sensitization followed by an allergic reaction may be observed.

Addiction. The gradual weakening of the effect of a drug, forcing an increase in the dose of the drug or replacing it with another, is called addiction. Sometimes the cause of addiction can be explained by accelerated processes of drug metabolism in the body. To some drugs, addiction develops very quickly. For example, with repeated administration of ephedrine at short intervals (20-30 minutes), a significant decrease in the vasoconstrictor effect is observed after 2-3 injections. This phenomenon is called tachyphylaxis(from the Greek tachys - fast, phylax- is - protection). Habituation should not be equated with drug dependence (addiction). These are completely different concepts.

Drug dependence (addiction). This phenomenon is characterized by a strong, sometimes irresistible, desire for the systematic use of certain medications and other substances that cause euphoria (a kind of intoxication, a pleasant mood). Euphoria can be caused by some substances that affect the psyche: morphine, heroin, cocaine, alcohol, hashish, nicotine, phenamine, etc. Most of these substances are drugs, so their systematic use in connection with drug dependence is called drug addiction. Addiction is usually combined with addictive phenomena, so the euphoric dose of the drug steadily increases, which leads to chronic poisoning of the body. Patients suffering from drug addiction are called drug addicts.

Currently, the term “bias” has been replaced by the concept "drug addiction ».

This definition shows that a drug (or other substance), during long-term use, becomes a necessary component of the cells of the central nervous system, and the body becomes dependent on this substance. Indeed, stopping drug use leads to severe subjective sensations and dysfunction of internal organs. These phenomena are called withdrawal symptoms(from Latin abstinentia - abstinence, deprivation), they quickly pass when taking the drug again.

There are mental and physical drug dependence. Mental drug dependence is accompanied by unpleasant emotional phenomena, depressed mood, and sometimes aggressiveness. With physical dependence, the drug addict’s condition is aggravated by dysfunction of the cardiovascular system and other organs. Acute cardiovascular failure (collapse) may occur.

Cumulation. As a result of slow metabolism or elimination of drugs in the body, their cumulation may occur (lat. sspilatio - accumulation). In such cases, repeated administration of drugs in therapeutic doses can lead to a significant increase in their concentration in the body (material cumulation) and poisoning.

There is also functional cumulation, when the effect of the previous medication is maintained and intensified with repeated doses. Cumulation can have a positive meaning, since it allows one to maintain the therapeutic effect of a drug for a long time when it is rarely introduced into the body.

For drugs that can cause accumulation, certain rules for use (breaks during treatment, gradual dose reduction) and dispensing from pharmacies have been established. Pharmacists should be aware of these rules and provide appropriate explanations to patients, especially in cases where the medicine is sold without a prescription. Failure to comply with the established rules can lead to severe poisoning.

Sensitization (increased sensitivity) of the body with repeated administration of drugs and the occurrence of allergic reactions are regarded as a pathological phenomenon and a complication of drug therapy.

A drug allergy is a peculiar reaction of the body to repeated administration of a drug, regardless of its dose. And the basis of an allergic reaction is immune processes. There are immediate (anaphylaxis) and delayed types of allergic reactions, characterized by a variety of symptoms: urticaria and other skin rashes, hematopoietic disorders, serum sickness, bronchial asthma, anaphylactic shock, etc.

The mutagenicity and carcinogenicity of some chemical compounds must be taken into account when creating new drugs. Mutagenicity - This is the ability of substances to cause permanent damage to the genetic apparatus of the germ cell, which manifests itself in a change in the genotype of the offspring. Carcinogenicity is the ability of substances to cause the development of malignant tumors.

With repeated administration of drugs, their effect can either increase or decrease. The increase in effect is associated with their accumulation in the body or organs. This phenomenon is called cumulation. Material cumulation occurs when a drug is slowly eliminated from the body and accumulates in it in toxic quantities, so the next administration of the drug should be carried out after its significant elimination or destruction.

Functional cumulation, when the effect accumulates, and not the substance, i.e. the next dose of medicine is received when the function of the organ or system has not yet recovered from the first administration. This can happen when some anticholinesterase drug is removed from the body or destroyed, and the amount of cholinesterase has not yet been restored to physiological levels. Then, with repeated administration of the drug, the function of the organs increases beyond the limits of possible physiological fluctuations, i.e., a toxic effect occurs.

The decrease in effect with repeated use of drugs is called addiction, i.e., tolerance to analgesics, laxatives and other drugs occurs. It may be associated with a decrease in the absorption of the substance, an increase in the rate of its inactivation and excretion, a decrease in the sensitivity of receptor formations to the substance, or a decrease in accumulation in the tissue.

One type of addiction is tachyphylaxis - addiction that occurs very quickly, sometimes after a single injection. For example, ephedrine, with frequent repeated administration (after 10-20 minutes), causes a smaller increase in blood pressure than with the first injection.

Some substances (usually neurotropic drugs) develop upon repeated administration. drug addiction. It manifests itself in people as an irresistible desire to repeat

taking a substance, usually with the aim of increasing mood, improving well-being, eliminating unpleasant experiences and sensations that arise when the effect of a previously administered substance ceases.

Idiosyncrasy- increased sensitivity to drugs. This happens after intravenous administration of iodine, bromine, and some antibiotics to small domestic animals, and to cats - phenol-containing substances.

2.10. Effect of drugs when administered in combination

In practical conditions, it is often necessary to administer to animals not one drug substance, but several at the same time, since one drug often does not provide the desired effect. There are cases when it acts for a short time or has not only a positive effect, but also a side effect, etc. For example, to obtain anesthesia, muscle relaxants are combined with inhaled or non-inhaled narcotic substances, local anesthetics with small doses of muscle relaxants, and a number of other combinations. The combined administration of medicinal substances that provide the osmotic pressure of the blood plasma, and therefore replace it (Ringerag-Locke solution), or a drug that improves digestion (artificial Carlsbad salt) has long been used; for angina pectoris, mixtures of cardiac, sedative and antispasmodic drugs (Watchal drops) are often used.

A combination of two or more similarly active substances is called synergy. If they act in the same direction, as a result of which a more pronounced effect is observed than when each of them is prescribed separately, and on the same system, we speak of direct m om s i n e r g i s m e (the effect of plant astringents and bismuth compounds in the intestines or hypnotics and non-inhalation narcotic substances). Indirect (indirect) synergism - when substances act in the same direction, but on different systems (pupil dilation with solutions of atropine and adrenaline).

If, when two drugs are administered, the pharmacological effect is higher than expected, then this phenomenon is called bytending(potentiation of the neuroleptic aminazine and the non-inhalation narcotic substance chloral hydrate when used in small doses).

Antagonism- the opposite effect of two or more substances, when one substance eliminates the effect of the other. It can be physical, chemical and physiological (direct and indirect).

Physical antagonism - when one substance introduced into the body creates a physical obstacle to the action of another drug. Thus, a solution of adrenaline, injected subcutaneously or otherwise, constricts blood vessels and thus prevents the absorption of other substances; activated carbon, adsorbing toxic substances in the gastrointestinal tract, prevents their absorption into the blood.

Chemical antagonism - when a drug reacts with another, the result is a substance that has no pharmacological activity. The action of antidotes is based on this. For example, acids are neutralized with alkalis, heavy metal compounds - with a solution of unithiol or calcium tetatsine or other substances.

However, physiological antagonism is most often possible, i.e., an opposite effect on the same physiological systems of the body. In this case, there is direct and indirect (indirect) antagonism. Spicy antagonism when two substances act oppositely on the same system (synapses, etc.) or organs. For example, atropine solution dilates the pupil, and pilocarpine constricts it, or the first substance relaxes the smooth muscles of the intestines, and the second contracts them. This happens because both substances act in the area of ​​the endings of cholinergic nerves (on the postsynaptic membrane of cholinergic synapses) in diametrically opposite ways, therefore the function of the innervated circular muscle of the iris changes differently. Or, for example, central nervous system stimulants and narcotic substances act differently - some stimulate the central nervous system, others depress it. This circumstance is used in veterinary practice in case of overdose of certain substances.

When two substances cause opposite effects in organ function, acting on different nerve structures or enzymes, then indirect antagonism appears. For example, the pupil narrows after applying carbacholin to the cornea (acts on cholinergic synapses in the circular muscle of the iris, which leads to its contraction - miosis), and adrenaline (acts in the area of ​​​​the endings of adrenergic nerve endings located in the radial muscles of the iris similar to their arousal) causes pupil dilation.

1. Addiction– gradual decrease in sensitivity to the action of the drug. For several months, years. Any substance is a xenobiotic.

2. Tachyphylaxis– rapid development of sensitivity to the action of the drug. A rare occurrence, but it does occur. Develops within 30 minutes. Ephedrine and reflex respiratory stimulants. It works in the presence of an intermediary substance.

3. Addiction/ drug dependence, mental and physical / drug addiction - an irresistible desire to take a drug. In the absence, the patient experiences withdrawal symptoms and withdrawal symptoms. Narcotic analgesics, sleeping pills, tranquilizers, alcohol.

4. Cumulation- accumulation of a medicinal substance in the body. a) material - the medicine accumulates in the body as such. b) functional - it is not the substance that accumulates, but its ether. Characteristic of ether alcohol.

5. Increased sensitivity.

A) ideosyncrosis- congenital or primary pathological sensitivity to the action of a drug. Genetic defect, enzyme deficiency. Fauvism - a reaction to the consumption of fava beans?, characteristic of the Mediterranean.

b) allergy/sensitization- occurs when repeated and subsequent contacts with a drug that acts as an allergen. For the formation of a classic allergic reaction, primary contact with the drug and the synthesis of antibodies in the body are required. Upon repeated administration, when the antigen interacts with the antibody, histamine is released, which determines the severity of the subsequent pathological reaction. Which can manifest itself from local manifestations to anaphylactic shock.

The most severe allergens are local anesthetics, antibiotics of a number of penicillins, sulfonamide derivatives.

Allergy sufferers should carry a dose of adrenaline with them to inject themselves if necessary.

Combined use of medicinal substances

The goal is to change the strength and severity of the pharmacological effect of medicinal substances. The combination can follow the principle of synergism (joint action) and antagonism.

At synergy may be observed:

a) the summation of effect is a simple arithmetic addition of two or more effects of medicinal substances.

b) potentiation - a significant increase in the effect of two or more drugs.

Neuroleptoanalgesia- a combination of a narcotic analgesic and a neuroleptic, which is used to treat psychiatric patients. This allows surgery to be performed without connecting the central nervous system.

Antagonism- a typical example: the use of antidotes, that is, antidotes for poisoning.

Classification of drug interactions

1. Physico-chemical. Activated carbon and toxins are a typical example.
2. Chemical interaction. Hydrochloric acid (stomach juice) and alkalis, in particular baking soda.
3. Pharmaceutical. Substances interact by direct contact. Furasimide does not interact well with other substances. Tetracycline in combination with milk forms insoluble compounds in the intestinal lumen. Eufillin should not be combined with glucose. B12 should also not be combined, except for ready-made preparations. ACC is also very aggressive.
4. Pharmacokinetic interaction.
5. Pharmacodynamic interaction.

Side effects

Side effects may include additional effects.

1. Recoil syndrome- exacerbation after rapid discontinuation of the drug, a sharp exacerbation of the underlying disease occurs. For example, clafilin. A potent medicine should not be stopped abruptly. Sleeping pills, glucocorticoids, interferon, etc. Discontinue gradually, reduce the dose by half, by a quarter.

1. Steal syndrome- against the background of the administration of vasodilators, deterioration of blood supply to the heart or brain occurs.

Repeated administrations of the same drug substance can lead to quantitative (increase or decrease) and qualitative changes in the pharmacological effect.

Among the phenomena observed with repeated administration of drugs, a distinction is made between accumulation, sensitization, addiction (tolerance) and drug dependence.

Cumulation (from lat. cumulation - increase, accumulation) - accumulation in the body of a pharmacologically active substance or the effects caused by it.

If, with each new administration of a drug, its concentration in the blood and/or tissues increases compared to the previous administration, this phenomenon is called material cumulation. Drugs that are slowly inactivated and slowly eliminated from the body, as well as drugs that are tightly bound to blood plasma proteins or in tissue depots, for example, some hypnotics from the barbiturate group, digitalis cardiac glycosides, can accumulate with repeated administrations. This can cause toxic effects, and therefore the dosage of such drugs should take into account their ability to accumulate.

If, with repeated administrations of a drug, an increase in the effect is observed without increasing the concentration of the substance in the blood and/or tissues, this phenomenon is called functional cumulation. This type of cumulation occurs with repeated drinking of alcohol. With the development of alcoholic psychosis (delirium tremens) in susceptible individuals, delusions and hallucinations develop at a time when ethyl alcohol has already been metabolized and is not detected in the body. However, at the same time, increasing changes in the function of the central nervous system occur. Functional cumulation is also characteristic of MAO inhibitors.

Sensitization. Many drugs form complexes with blood plasma proteins, which under certain conditions acquire antigenic properties. This is accompanied by the formation of antibodies and sensitization. Repeated introduction of the same medicinal substances into a sensitized organism is manifested by allergic reactions. Often such reactions occur with repeated administration of penicillins, procaine, water-soluble vitamins, sulfonamides, etc.

Habituation (tolerance, from lat. tolerance- patience) - a decrease in the pharmacological effect with repeated administrations of a medicinal substance in the same dose. Addiction may be due to changes in the pharmacokinetics of the drug (decreased absorption, increased rate of metabolism and excretion), as well as a decrease in the sensitivity of receptors and/or a decrease in their density on the postsynaptic membrane. For example, addiction to barbiturates may be a consequence of an increase in the intensity of their metabolism due to the induction of enzymes under the influence of the barbiturates themselves. Addiction to medications can develop over a period of several days to several months. In case of addiction, to obtain the same pharmacological effect, it is necessary to increase the dose of the drug, which can lead to increased side effects. Therefore, they often take a break from using this substance, and if it is necessary to continue treatment, drugs with a similar effect, but from a different chemical group, are prescribed. When one substance is replaced by another, regardless of its chemical structure, cross-addiction may occur if the substances interact with the same substrate (such as a receptor or enzyme)

A special case of addiction is tachyphylaxis (from the Greek. tachys- fast, phytaxis- protection) - rapid development of addiction with repeated administration of the drug at short intervals (10-15 minutes). Tachyphylaxis to ephedrine is well known, which is caused by depletion of norepinephrine reserves in the endings of sympathetic nerve fibers. With each subsequent administration of ephedrine, the amount of norepinephrine released into the synaptic cleft decreases and the hypertensive effect of the drug (increase in blood pressure) after the 2nd or 3rd administration decreases.

Another special case of addiction is mithridatism - the gradual development of insensitivity to the effects of drugs and poisons, which occurs with prolonged use, first in very small and then in increasing doses. According to ancient Greek legend, King Mithridates thus acquired insensitivity to many poisons.

With repeated use of certain substances that cause extremely pleasant sensations (euphoria), predisposed individuals develop drug dependence.

Drug dependence is an urgent need (irresistible desire) for constant or periodically renewed use of a certain medicinal substance or group of substances.

Initially, the use is associated with the goal of achieving a state of euphoria, to eliminate painful experiences and sensations, to achieve a feeling of well-being and comfort, to obtain new sensations during the development of hallucinations. However, after a certain time, the need for repeated use becomes insurmountable, which is aggravated by withdrawal syndrome - the occurrence of a serious condition when stopping taking a given substance, associated not only with changes in the mental sphere, but also with somatic disorders (impaired functions of organs and systems of the body). This condition is referred to as “abstinence” (from Lat. abstinentia - abstinence).

There are mental and physical drug dependence.

Mental drug dependence is characterized by a sharp deterioration in mood and emotional discomfort, a feeling of fatigue when deprived of the drug. Occurs when using cocaine and other psychostimulants (amphetamine), hallucinogens (lysergic acid diethylamide - LSD-25), nicotine, Indian hemp (anasha, hashish, plan, marijuana).

Physical drug dependence is characterized not only by emotional discomfort, but also by the occurrence of withdrawal symptoms.

Physical drug dependence develops to opioids (heroin, morphine), barbiturates, benzodiazepines, alcohol (ethyl alcohol). , at Drug dependence is often combined with addiction, requiring increasingly larger doses of the substance to produce euphoria. The most severe drug dependence occurs in the case of a combination of mental dependence, physical dependence and addiction.

The use of substances for the purpose of obtaining an intoxicating effect is called substance abuse.

Drug addiction is a special case of substance abuse, when a substance included in the list of substances causing drug dependence (narcotic substances) and subject to control is used as an intoxicant.

With repeated administration of drugs, their effect can either increase or decrease.

An increase in effect may be due to the accumulation of medicinal substances in the body or in individual organs - cumulation . It can be material and functional.

Material cumulation– the drug is slowly eliminated from the body and, with repeated administration, accumulates in it, reaching toxic quantities. To avoid this, repeat administration should be administered after a significant portion of the elimination or destruction of the previous dose. Functional cumulation– when the initially introduced substance is removed from the body, and the function of the organ or system altered by it has not yet been restored. If a repeated dose of the medicine is administered at this time, its effect is much more pronounced and lasts longer.

addictive– decrease in effect with repeated use of the drug. It may be associated with a decrease in the absorption of the substance, an increase in the rate of its elimination from the body, and a decrease in the sensitivity of receptors.

Dependence (addiction)) – an irresistible urge to re-admit. People have mental and physical. Mental – emotional discomfort without medication

Physical – when the drug is discontinued, a serious condition occurs associated with a disorder of the functions of organs and systems.

Idiosyncrasy– genetically determined hypersensitivity to any drug. Happens after using iodine supplements for pets,

Question 25 of the ticket: addiction to medicinal substances upon repeated administration:

addictive(tolerance, lat. tolerantis - patience) is a decrease in sensitivity to the drug after its repeated administration, which requires an increase in the dose in order to cause an effect of the same intensity that occurred after the administration of a smaller dose. addictive- this is a partial or complete loss of the therapeutic (medicinal) effect during long-term use of a drug without the phenomena of drug dependence, that is, the development of addiction. For example, with the introduction of herbal laxatives containing anthraglycosides (rhubarb root, buckthorn bark, hay leaves), the laxative effect decreases after a few weeks. Habituation is a general biological property that can also be observed in microorganisms after the use of small doses of chemotherapy drugs. Addiction can be eliminated either by increasing (within available limits) the dose, or by replacing the drug or stopping its use for a while.

A rapid decrease in the effectiveness of a drug after repeated administration, which develops over a period of time from several minutes to one day, is called tachyphylaxis(from Greek tachys - fast and phylaxis - protection). An example of tachyphylaxis would be a decrease in the hypertensive effect of ephedrine. After the first administration of the drug, blood pressure increases; after repeated 2-3 injections with an interval of 20-30 minutes, the vasoconstrictor effect is significantly reduced. More often than not, addiction to the drug develops slowly, over several weeks of constant use. Sleeping pills (especially barbituric acid derivatives), tranquilizers, narcotic analgesics, laxatives, etc. have addictive properties. Drugs that are similar in chemical structure can also be addictive (promedol, morphine). Tolerance mechanisms are different . It is a widely known fact arsenophagy- the ability of “trained” animals to ingest large amounts of arsenic oxide without harmful consequences. In this case, addiction is caused by the development of inflammatory processes in the mucous membrane of the digestive canal and, as a result, a decrease in the absorption of poison. If arsene oxide is administered parenterally to such an animal, even a minimal dose will be lethal.

The most common cause of addiction is the induction of microsomal liver enzymes by the drug and the acceleration of its own metabolism. This mechanism predominates in the development of addiction to barbiturates. Tolerance to organophosphorus compounds is due to a decrease in the sensitivity of cholinergic receptors to acetylcholine. The cause of addiction may also be the phenomenon of autoinhibition, similar to the phenomenon of enzyme inhibition by a substrate, known in biochemistry. The essence of the phenomenon is that in case of excess of the drug in the body, not one, but several molecules bind to the receptor. The receptor is “overloaded” and the pharmacological effect is significantly less. Tolerance should not be equated with drug dependence.

Dependence on drugs and other substances (addiction). According to the findings of the WHO Expert Committee, drug dependence is a mental condition, sometimes even physical, that results from the interaction between a living organism and a drug substance with certain behavioral and other reactions, when the desire to take the drug is constant or occurs periodically in order to avoid the discomfort that arises without accepting it.

Addiction- this is a strong, sometimes irresistible requirement for the systematic use of certain medications and other drugs that cause euphoria (Greek eu - pleasant and phero - to endure), to improve mood, improve well-being, and also eliminate the unpleasant sensations that arise after the withdrawal of these drugs.

Drugs that cause addiction can be divided into the following groups: alcohol-barbiturate (ethyl alcohol, phenobarbital); Cannabine (marijuana, hashish); cocaine; ethereal solvents (toluene, acetone, carbon tetrachloride); drugs that cause hallucinations (LSD, mescaline, psilocybin); drugs derived from opium (morphine, codeine, heroin) and their synthetic substitutes (promedol, fentanyl).

It is possible to become dependent on multiple substances at the same time.

There are mental and physical dependence on drugs. According to the WHO definition, mental dependence is “a state in which a drug produces a feeling of satisfaction and mental exaltation - a state of euphoria that requires periodic or continuous administration of the drug to obtain a feeling of satisfaction in order to avoid discomfort”; physical dependence is an adaptive condition characterized by intense physical distress after stopping a particular drug. These disorders, i.e. withdrawal syndrome(Latin abstinentia - abstinence; synonym withdrawal syndrome, deprivation) - a complex of specific signs of mental and physical disorders characteristic of a particular narcotic analgesic.

The mechanism of this phenomenon is due to the fact that, due to systematic administration, the substance is included in the biochemical processes occurring in the body.

As a result, metabolism and tissue function are altered. The body gradually adapts to this state, creating a new metabolic homeostasis that differs from the usual one. If the supply of the drug is stopped, the balance of biochemical processes is disrupted. A serious condition (withdrawal) occurs - various, often severe somatic disorders (death is possible) - which is eliminated only with the resumption of administration of the substance.

Brain cells are the most sensitive to changed conditions, which is why drug addiction is caused by drugs that affect the central nervous system. The systematic use of narcotic analgesics with the development of dependence is called drug addiction. Changes in brain function lead to the sequential development of states of euphoric sleep and withdrawal. As addiction increases, the euphoric phase shortens, the sleep phase almost disappears, and the withdrawal phase changes and deepens. The most severe picture of drug dependence develops when physical, mental dependence and tolerance are combined.

Ticket question 26: drug addiction:

Drug addiction- a syndrome that develops with repeated long-term use of drugs and is manifested by a sharp deterioration in health or well-being when the drug is discontinued. The best known is dependence on psychotropic drugs, often associated with withdrawal symptoms, for example, when withdrawing from opiates or psychostimulants. However, dependence on many other drugs, such as glucocorticosteroids, is known. In persons with neurotic, somatoform and anxiety-depressive disorders, with persistent insomnia, after the prescription of sedatives and hypnotics, dependence can form (in approximately 10% of cases) - an attempt to stop taking them leads to an exacerbation of symptoms. Drug dependence when taking benzodiazepines is widespread, primarily due to the unreasonable duration of their use: with short-term use, the risk of dependence is reduced.

Withdrawal syndrome of psychopharmacological drugs can be considered as a variant of withdrawal syndrome in drug addiction, but it has a number of significant differences. The closest thing to withdrawal syndrome is tranquilizer withdrawal syndrome: in this case, manifestations of physical and mental dependence are observed, although mental dependence in the form of craving for the drug rarely occurs - the so-called psychological attachment is more often present. When antidepressants are discontinued, only physical dependence is present: a characteristic vegetative symptom complex occurs, and when antipsychotics are discontinued, physical dependence is also observed (vegetative symptom complex and extrapyramidal disorders) without mental dependence. Long-term use of antipsychotics and antidepressants usually also does not cause changes in drug tolerance.

Drug dependence can be overcome by abrupt (in the case of mental dependence) or gradual withdrawal of the drug or by replacing the drug with a less addictive one.( Addiction(English) addiction- addiction, addiction, addiction), in a broad sense, is an obsessive need felt by a person for a certain activity. The term is often used for such phenomena as drug addiction, drug addiction, but now it is more applied to non-chemical, but psychological addictions, for example, behavioral, examples of which are: Internet addiction, gambling addiction, shopaholism, psychogenic overeating, fanaticism, etc. .

In a medical sense, addiction is obsessive the need to repeat certain actions, accompanied, in the event of a violation of the patient’s usual schedule, by clearly expressed physiological and psychological deviations, non-trivial behavior and other mental disorders.

Ticket question 27: the phenomenon of synergism and antagonism of medicinal substances:

Synergism is a type of interaction in which the effect of the combination exceeds the sum of the effects of each of the substances taken separately. That is 1+1=3 . Synergism can relate to both desired (therapeutic) and undesirable effects of drugs. The combined administration of the thiazide diuretic dichlorothiazide and the ACE inhibitor enalapril leads to an increase in the hypotensive effect of each drug, which is used in the treatment of hypertension. However, the simultaneous administration of aminoglycoside antibiotics (gentamicin) and the loop diuretic furosemide causes a sharp increase in the risk of ototoxicity and the development of deafness.

SYNERGISM OF MEDICINES (from the Greek synergia - cooperation, assistance), simultaneous action in one direction of two or more. substances that provide a higher overall effect than the action of each of them separately. Medicines substances can act on the same elements (direct S. l.s.) or on different ones (indirect S. l.s.). An example of direct S. l. With. can serve as a narcotic. the effect of chloralhydrite and alcohol, indirect - dilation of the pupil with atropine and adrenaline. As a result of the joint action of pharmacological synergists. the effect is of unequal strength, which depends on the properties of the substances, their doses and characteristics of the patol. state of the body. S. l. is most fully expressed. With. with a combination of substances in small doses, as well as with a combination of substances acting on different systems.

With a combination of certain medications. substances, you can get an increase in the effect of one or more of them (for example, aminazine enhances the narcotic effect of chloral hydrate). This phenomenon is called potentiation. When both substances affect the same body systems and in the same direction (for example, potentiation of barbiturate anesthesia with chlorpromazine), potentiation of cash. true. In contrast, with false potentiation it will help. the substance does not have an active pharmacological effect. action, but only weakens the decay or slows down the release of the basic. substances (eg, prolongation of barbiturate anesthesia with chloracyzine). Therefore, false potentiation is one of the forms of prolongation (long-term action)

The effect of summation of the action of drugs is used in practical medicine to reduce the possible occurrence of unwanted side effects, since the lower the dose, the less likely it is to develop undesirable effects.

Antagonism(from the Greek anti- against, agon- fight) drugs in combinations manifest themselves in the weakening or complete disappearance of their pharmacotherapeutic effect. In medicine, antagonism as a type of pharmacological incompatibility can be divided into physicochemical and physiological. Physico-chemical include the so-called competitive, physical and chemical antagonisms (pharmaceutical incompatibility); to the physiological - direct and indirect (pharmacological incompatibility).

Physical antagonism in pharmacology is possible between adsorbents (activated carbon, proteins, bentonite) and active medicinal substances, the effect of which is eliminated due to their adsorption on adsorbents.

Physical and chemical antagonists in practice are more often used as antidotes, or antidotes (from the Greek antidotos - antidote). Thus, in case of barium chloride poisoning, sodium sulfate can be used as an antidote; heavy metals are firmly bound and neutralized by unithiol, etc.

With the simultaneous use of several medicinal substances, it is possible to completely turn off or weaken the effect of some substances by others.

This phenomenon is called pharmacological antagonism. It is generally considered to be based on the presence of competitive relationships or changes in the background for the action of substances.

Like synergism, antagonism can be direct and indirect. In the first case, medicinal substances have the same object of action, and in the second, the objects are different.

For example, a pupil constricted by arecoline can be dilated with atropine or adrenaline.

Atropine and arecoline act through the same entity (cholinergic nerves) and therefore their antagonism is direct.

The opposite effect of arecoline and adrenaline is obtained due to the effect on different objects (adrenergic and cholinergic nerves), but directly related to the same function (pupil size), so their antagonism is indirect. Antagonists can act to the same extent (bilateral antagonism) or in different ways, when the influence of one of them prevails over the other (one-sided antagonism).

Since the limiting stage of pharmacological action is paralysis, paralyzing substances are one-sided antagonists in any combination. Exciting and depressing substances can act antagonistically, either bilaterally or unilaterally, depending on the properties of the antagonists.

Ticket question 28:sources of medicinal substances :

These include minerals, plant raw materials, raw materials of animal origin, waste products of microorganisms, synthetic compounds

Mineral springs- these are purified various chemical compounds: iron, copper, iodine, manganese, bismuth, cobalt, sodium, etc.

Animal origin- these are drugs obtained from animal organs and tissues: adrenaline, insulin, hormone preparations of the adrenal glands, pituitary gland, enzyme preparations, venoms of snakes, spiders, bees (antibiotics of animal origin).

Herbal medicinal substances Sources of medicinal substances can be fruits, flowers, leaves, bark, roots, rhizomes of various plants. According to their chemical structure, these are different compounds:

Alkaloids (alcalos - alkali). These are nitrogenous alkali-like substances that can contain oxygen and be oxygen-free - caffeine, nicotine, atropine, strychnine, etc.

Glycosides are ester-like substances that contain the non-sugar substance aglycone and the sugar glycone. Such preparations are obtained from various types of foxglove, lily of the valley, Montenegrin, strophanthus, etc.

Resins are compounds insoluble in water (soluble in organic solvents). With alkalis they form soap-like compounds - sabur.

Comedy - These are mucus and mucus-like substances containing carbohydrates. Hydrolysis produces sugars. In water, mucus has an enveloping effect.

Fixed oils- castor, sunflower, flaxseed, etc.

Essential oils- volatile aromatic compounds: dill, caraway, mustard, clove, mint, etc. (expectorants, emetics).

Tannins- nitrogen-free compounds that have a local effect (oak bark, blueberries, sage).

Ticket question 29: sources of medication dosage:

Age. The body's sensitivity to drugs changes with age. Children and older people over 60 are more sensitive to the effects of drugs compared to middle-aged people.

Body mass. Children are prescribed a lower dose of the drug than adults due to the fact that they have less body weight. And the greater a person’s body weight, the greater the dosage they are prescribed.

Individual sensitivity. The same drugs can act differently on different people, even if it is the same dosage. The effect of l/p may vary depending on the pathological state of the body. Some pharmacological agents exhibit their effect only in pathological conditions (for example, acetylsalicylic acid, lowers body temperature only if it increases, cardiac glycosides clearly stimulate the activity of the heart only in heart failure)

Ticket question 30: complications of drug therapy:

Complications of drug therapy are changes caused by medicinal substances in the properties and functions of organs and systems of the body, accompanied by unpleasant subjective sensations or objectively threatening the health or life of the patient. They are caused by side, toxic or nonspecific effects of drugs.

A side effect is considered to be the effect of a drug, which has the same mechanism of occurrence as the main one, but is not desirable from a therapeutic point of view. There are no drugs that do not have side effects. Thus, the administration of the adrenergic agonist adrenaline hydrochloride as a bronchodilator causes tachycardia and increased blood pressure. A common side effect of chemotherapeutic agents is the suppression of the vital activity of not only the causative agent of the infectious disease, but also of commensal microorganisms. When the vital activity of microorganisms sensitive to a drug is suppressed, species insensitive to it (cocci, bacteria, fungi) multiply intensively (drug-induced dysbacteriosis, candidiasis).

Phytoncides - antibiotics of plant origin (onion, garlic, wild garlic, bird cherry, nettle, etc.)

Microorganisms are producers of many medicinal substances: antibiotics, enzyme preparations, etc. Preparations of fungal origin are also widespread - antibiotics.

Synthetic drugs- these are drugs that are obtained in the laboratory through chemical reactions: FOS, COS, carbamates, antibiotics, sulfonamides, hormonal, enzymatic, etc.

Side effects become complications if they cause patient complaints or pose a threat to health or life. For example, when treating bronchial asthma with atropine, the resulting dry mouth can reach such a degree that it makes swallowing and/or speech difficult. A side effect of this degree is assessed as a complication of drug therapy and requires the adoption of measures aimed at eliminating this complication, in particular drug withdrawal. These complications are dose-dependent, easily predictable, and their manifestations are most often mild in severity. In order to prevent them, it is necessary, firstly, to use drugs with maximum selectivity of action. For example, relief of bronchospasm with the mixed adrenergic agonist adrenaline is accompanied by an increase in blood pressure and tachycardia, but the non-selective beta-adrenergic agonist isadrin causes only tachycardia, and the selective beta 2-adrenergic agonist fenoterol (Berotec) does not cause either an increase in blood pressure or significant tachycardia.

Complications of a toxic nature most often have a different mechanism of occurrence than the main effect. For example, the suppression of hematopoiesis that occurs during treatment with butadione is not due to COX blockade. Toxic complications are often the result of drug overdose, including those caused by material or functional cumulation during long-term use of even therapeutic doses (chronoconcentration effect.). In this case, a predominant toxic damage to one or a group of organs (systems) is usually observed, and therefore neurotoxic, cardiotoxic, etc. are distinguished. action of the drug.

Among the adverse reactions when using drugs, the most common are those caused by their pharmacological properties when the drug is used in a therapeutic dose. For example, redness of the skin when using nicotinic acid is a common and normal reaction, although it is a side effect, or tricyclic antidepressants and chlorpromazine not only have an effect on the central nervous system, but also cause dry mouth and double vision.

For some drugs, toxic complications cannot be avoided at all. For example, cytostatics not only suppress the growth of tumor cells, but also damage all rapidly dividing cells and suppress the bone marrow. Therefore, in addition to their direct effect, they naturally lead to leukopenia.

With an increase in the dose of drugs, the risk of adverse reactions increases, for example, leukopenia develops from taking cytostatics, and the sedative effect of antihistamines increases.

Diseases of the cardiovascular system are the determining cause of death in people, and hypertension plays a primary role in this. Therefore, millions of people are being treated for hypertension and coronary heart disease. Beta blockers and calcium channel blockers are primarily used for therapy. During therapy, several variants of clinical forms of adverse reactions associated with the pharmacological activity of the drug are observed. Beta blockers, reserpine, methyldopa, clonidine cause depression. Therefore, propranolol (Anaprilin), which is especially associated with depression, should not be used by people suffering from depression or who have suffered from it in the past. Atenolol and nadolol are less likely to cause such side effects. Fatigue is often caused by beta blockers, reserpine, methyldopa, and clonidine. Beta blockers, methyldopa and a number of other drugs in the treatment of pathologies of the cardiovascular system cause impotence and other types of sexual dysfunction. Often, when taking antihypertensive drugs, especially guanitidine, prazosin and methyldopa, dizziness is observed and, as a result, orthostatic hypotension occurs when suddenly rising from a sitting or lying position. This can lead to falls and fractures. Among beta blockers, labetalol most often causes dizziness and a decrease in blood pressure, which makes it a second-line drug in the treatment of uncomplicated hypertension. Beta blockers can cause bronchospasm and provoke asthma attacks, so they should not be used by people with asthma, chronic bronchitis or emphysema.