Antagonism (biology): characteristics and types. Drug interactions Antagonism of drugs

SYNERGISM, the combined effect of two drugs, which is stronger than the sum of the actions of these two drugs when used separately. 2) synergism - a type of interaction in which the effect of the combination exceeds the sum of the effects of each of the substances taken separately.

1. A variant of the body’s reaction to the combined effects of two or more drugs, characterized by the fact that the resulting effect exceeds the effect of each component separately. In medicine, synergism (from the Latin synergia) is the promotion, joint action of drugs in one direction.

An example of synergism is the combined use of any sulfonamide with trimethoprim. Another example of synergism is the use of aminazine and any barbiturate in combination.

An example of the first combination is the anti-blastoma cyclophosphamide and one of any glycans (for example, rodexman). Secondary in vivo reactions may occur due to drug antagonism, pharmacological or pharmaceutical incompatibility in combinations, and for other reasons. That is, 1+1=3. Synergism can relate to both desired (therapeutic) and undesirable effects of drugs.

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It will displace the antagonist from the active center of the receptor and cause a full tissue response. Losartan is a competitive antagonist for angiotensin AT1 receptors; it disrupts the interaction of angiotensin II with receptors and helps lower blood pressure.

3) Physiological (indirect) antagonism - antagonism associated with the influence of 2 drugs on various receptors (targets) in tissues, which leads to a mutual weakening of their effect. The following types of synergism are distinguished: additive action (simple summation of effects), potentiation (significant enhancement of effects), direct synergism, indirect synergism.

Antagonism associated with the chemical or physicochemical interaction of two substances is designated as antidote, and substances that weaken the effect of other substances according to this principle are called antidotes. When prescribing one or more drugs, you need to make sure that there is no antagonistic effect between them; which precludes their simultaneous use.

Antagonism can also be direct and indirect

With rational combination, it is possible to reduce the doses of active medicinal substances, as a result of which unwanted side effects are reduced or do not appear. If two or more medicinal substances are simultaneously introduced into the body, their combined effect is obtained. In some cases, the effect of one medicine does not affect the effect of another. If medicinal substances act in one direction, then we are dealing with synergy.

If the effect of the combination exceeds the sum of the individual effects, then this phenomenon is called potentiation (multiplication). It is generally accepted that substances with the same mechanism of action have additive synergism, while potentiation is provided by substances with different mechanisms.

The effect of two medicinal substances can be opposite and mutually weaken. In addition, a distinction is made between unilateral antagonism, when the effect of one drug cancels the effect of the other, but not vice versa, and bilateral, when any of the two substances neutralizes the effect of the other.

Antagonism can also depend on two substances reacting chemically and neutralizing each other. It will be a chemical antagonism. Antagonism of drugs is used in the fight against poisoning.

SYNERGISM - (new Latin, from Greek synergia assistance). Synergy is a phenomenon when the total effect of two or more factors exceeds the sum of the influence of individual factors. See also Drug compatibility. At the same time, they strive to get a better effect from a combination of drugs than from each one separately. Each medicinal substance acts on different parts of the brain, and therefore the overall effect is more profound.

An example of the 2nd combination is the anti-tuberculosis drugs rifampicin and ethambutol. Finally, an example of a 3rd combination would be a combination of antibiotics (cephalexin + ampicillin) against sensitive bacteria. Chemical antagonism underlies the action of antidotes (antidotes). Since the degree of binding of a substance to the receptor is proportional to the concentration of this substance, the effect of a competitive antagonist can be overcome by increasing the concentration of the agonist.

When the action of synergists is aimed at the same cellular elements, then the synergism is called true, or direct; otherwise they talk about indirect, or indirect, synergism

That. a competitive antagonist does not change the maximum effect of the agonist, but a higher concentration of the agonist is required for the interaction of the agonist with the receptor. In medical practice, competitive antagonism is often used.

Synergism (in pharmacology) is the phenomenon of mutual enhancement of the effectiveness of the main and (or) side effects of drugs when used together. 2) Pharmacological (direct) antagonism - antagonism caused by the multidirectional action of 2 drugs on the same receptors in tissues. A) competitive antagonism: a competitive antagonist reversibly binds to the active center of the receptor, i.e., shields it from the action of the agonist.

When drugs interact, the following conditions may develop: a) increased effects of a combination of drugs b) weakened effects of a combination of drugs c) drug incompatibility

Strengthening the effects of a drug combination is implemented in three options:

1) summation of effects or additive interaction– a type of drug interaction in which the effect of the combination is equal to the simple sum of the effects of each drug separately. Those. 1+1=2 . Characteristic of drugs from the same pharmacological group that have a common target of action (the acid-neutralizing activity of the combination of aluminum and magnesium hydroxide is equal to the sum of their acid-neutralizing abilities separately)

2) synergism - a type of interaction in which the effect of the combination exceeds the sum of the effects of each of the substances taken separately. Those. 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.

3) potentiation - a type of drug interaction in which one of the drugs, which by itself does not have this effect, can lead to a sharp increase in the effect of another drug. Those. 1+0=3 (clavulanic acid does not have an antimicrobial effect, but can enhance the effect of the β-lactam antibiotic amoxicillin due to the fact that it blocks β-lactamase; adrenaline does not have a local anesthetic effect, but when added to the ultracaine solution, it sharply prolongs its anesthetic effect by slowing down absorption anesthetic from the injection site).

Reducing Effects Drugs when used together are called antagonism:

1) chemical antagonism or antidotism– chemical interaction of substances with each other with the formation of inactive products (the chemical antagonist of iron ions deferoxamine, which binds them into inactive complexes; protamine sulfate, the molecule of which has an excess positive charge - the chemical antagonist of heparin, the molecule of which has an excess negative charge). Chemical antagonism underlies the action of antidotes (antidotes).

2) pharmacological (direct) antagonism- antagonism caused by the multidirectional action of 2 drugs on the same receptors in tissues. Pharmacological antagonism can be competitive (reversible) or non-competitive (irreversible):

a) competitive antagonism: a competitive antagonist reversibly binds to the active site of the receptor, i.e. shields it from the action of the agonist. Because The degree of binding of a substance to the receptor is proportional to the concentration of this substance, then the effect of a competitive antagonist can be overcome by increasing the concentration of the agonist. It will displace the antagonist from the active center of the receptor and cause a full tissue response. That. a competitive antagonist does not change the maximum effect of the agonist, but a higher concentration of the agonist is required for the interaction of the agonist with the receptor. Competitive antagonist shifts the dose-response curve for the agonist to the right relative to the initial values ​​and increases the EC 50 for the agonist, without affecting the value of E max .

In medical practice, competitive antagonism is often used. Since the effect of a competitive antagonist can be overcome if its concentration falls below the level of the agonist, during treatment with competitive antagonists it is necessary to constantly maintain its level sufficiently high. In other words, the clinical effect of a competitive antagonist will depend on its half-life and the concentration of the full agonist.

b) non-competitive antagonism: a non-competitive antagonist binds almost irreversibly to the active center of the receptor or generally interacts with its allosteric center. Therefore, no matter how much the concentration of the agonist increases, it is not able to displace the antagonist from its connection with the receptor. Since some of the receptors that are associated with a non-competitive antagonist are no longer able to activate , E value max decreases, but the affinity of the receptor for the agonist does not change, so the EC value 50 remains the same. On a dose-response curve, the effect of a non-competitive antagonist appears as a compression of the curve relative to the vertical axis without shifting it to the right.

Scheme 9. Types of antagonism.

A – a competitive antagonist shifts the dose-effect curve to the right, i.e. reduces the sensitivity of the tissue to the agonist without changing its effect. B - a non-competitive antagonist reduces the magnitude of the tissue response (effect), but does not affect its sensitivity to the agonist. C – option of using a partial agonist against the background of a full agonist. As the concentration increases, the partial agonist displaces the full one from the receptors and, as a result, the tissue response decreases from the maximum response to the full agonist to the maximum response to the partial agonist.

Non-competitive antagonists are used less frequently in medical practice. On the one hand, they have an undoubted advantage, because their effect cannot be overcome after binding to the receptor, and therefore does not depend either on the half-life of the antagonist or on the level of the agonist in the body. The effect of a non-competitive antagonist will be determined only by the rate of synthesis of new receptors. But on the other hand, if an overdose of this medicine occurs, it will be extremely difficult to eliminate its effect.

Losartan is a competitive antagonist for angiotensin AT 1 receptors; it disrupts the interaction of angiotensin II with receptors and helps lower blood pressure. The effect of losartan can be overcome by administering a high dose of angiotensin II. Valsartan is a non-competitive antagonist for these same AT 1 receptors. Its effect cannot be overcome even with the administration of high doses of angiotensin II.

Of interest is the interaction that takes place between full and partial receptor agonists. If the concentration of the full agonist exceeds the level of the partial agonist, then a maximum response is observed in the tissue. If the level of a partial agonist begins to increase, it displaces the full agonist from binding to the receptor and the tissue response begins to decrease from the maximum for the full agonist to the maximum for the partial agonist (i.e., the level at which it occupies all receptors).

3) physiological (indirect) antagonism– antagonism associated with the influence of 2 drugs on various receptors (targets) in tissues, which leads to a mutual weakening of their effect. For example, physiological antagonism is observed between insulin and adrenaline. Insulin activates insulin receptors, as a result of which the transport of glucose into the cell increases and the glycemic level decreases. Adrenaline activates  2 -adrenergic receptors in the liver and skeletal muscles and stimulates the breakdown of glycogen, which ultimately leads to an increase in glucose levels. This type of antagonism is often used in emergency care of patients with an insulin overdose that has led to hypoglycemic coma.

Interactions of substances (amino acids, vitamins, drugs) in the body, characterized by the fact that one of them weakens the effect of the other.

Absolute antagonism- A., in which the effect of the combined action of substances is less than the effect of each of them acting separately.

Bilateral antagonism- A., in which any of two substances weakens or removes the effect of the other.

Competitive antagonism- direct A., in which substances reversibly interact with the same cell receptors.

Indirect antagonism- cm. Antagonism indirect.

Antagonism is non-competitive- direct A., in which one of the interacting substances acts outside its active center.

Indirect antagonism(A. indirect) - A., in which the action of substances is directed to different cellular elements.

Antagonism is unbalanced- A., in which one of the substances interacts with receptors irreversibly.

One-sided antagonism- A., in which the effect of one substance cancels the effect of another, but not vice versa.

Antagonism is relative- A., in which the effect of the combined action of substances is greater than the individual effects of each of them, but less than the sum of the effects of the same substances acting separately.

Direct antagonism- A., in which the action of substances is aimed at the same cellular elements.

1. Small medical encyclopedia. - M.: Medical encyclopedia. 1991-96 2. First aid. - M.: Great Russian Encyclopedia. 1994 3. Encyclopedic Dictionary of Medical Terms. - M.: Soviet Encyclopedia. - 1982-1984.

Antonyms:

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- (from the Greek antahonisma dispute, struggle) a contradiction, which is characterized by an acute irreconcilable struggle between warring forces and tendencies. The term "A." used in religious systems, in relation to the struggle between good and evil, in philosophy. teachings of I. Kant, A.... ... Philosophical Encyclopedia

- (from the Greek anti against, and agonizomai I fight). Hostility, disagreement in opinions, struggle, opposition. Dictionary of foreign words included in the Russian language. Chudinov A.N., 1910. ANTAGONISM from the Greek. anti, against, and agonizomai, I fight. Persecution... Dictionary of foreign words of the Russian language

antagonism- a m. antagonisme m. gr. antagonisma dispute, struggle. 1. Irreconcilable contradiction. SIS 1985. Intransigence in views, views, etc. on anything, hostility of positions, relationships. BAS 2. It seems to me that there is nothing in communism and socialism... ... Historical Dictionary of Gallicisms of the Russian Language

Enmity, rivalry, hostility, opposition, dislike, ill will. . .. Cm … Synonym dictionary

ANTAGONISM, antagonism, plural. no, husband (Greek: antagonismos). Rivalry, mutual struggle of interests. The antagonism between Europe and America has taken new forms in recent years. Class antagonism in capitalist countries is intensifying. || Hostile... ... Ushakov's Explanatory Dictionary

ANTAGONISM- (from the Greek anti against and agon struggle), a term used to define the negative interaction or opposition of two phenomena or organisms; expressed either directly in their mutual destruction or weakening, or indirectly in... ... Great Medical Encyclopedia

The relationship of microorganisms in natural or laboratory conditions, in which one species delays or completely suppresses the growth of another. Antagonists can be representatives of all groups of microorganisms. With passive A. oppression of a competitor ... Dictionary of microbiology

- (from the gr. antagonisma - dispute, struggle) - an irreconcilable contradiction in culture - antagonism between the bearers of mutually exclusive social programs of behavior, worldviews (humanism and misanthropy, nationalism and ... ... Encyclopedia of Cultural Studies

- (from the Greek antagonisma dispute, struggle), a contradiction characterized by an acute struggle of hostile forces, tendencies ... Modern encyclopedia

- (from the Greek antagonisma dispute struggle), a contradiction characterized by an acute struggle of hostile forces, tendencies ... Big Encyclopedic Dictionary

ANTAGONISM, huh, husband. An irreconcilable contradiction. A. views. | adj. antagonistic, oh, oh. Ozhegov's explanatory dictionary. S.I. Ozhegov, N.Yu. Shvedova. 1949 1992 … Ozhegov's Explanatory Dictionary

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When drugs are used in combination, their effect may be enhanced (synergism) or weakened (antagonism).

Synergism (from the Greek syn - together, erg - work) is the unidirectional action of two or more drugs, in which a pharmacological effect develops stronger than that of each substance separately. Drug synergism occurs in two forms: summation and potentiation of effects.

If the severity of the effect of the combined use of a drug is equal to the sum of the effects of the individual substances included in the combination, the effect is defined as a summation, or additive effect. Summation occurs when drugs are introduced into the body that affect the same substrates (receptors, cells

When one substance significantly enhances the pharmacological effect of another substance, the interaction is called potentiation. With potentiation, the total effect of the combination of two substances exceeds the sum of the effects of each.

Drugs can act on the same substrate (direct synergism) or have different localization of action (indirect synergism).

Antagonism (from the Greek anti - against, agon - fight) is a reduction or complete elimination of the pharmacological effect of one drug by another when they are used together. The phenomenon of antagonism is used in the treatment of poisoning and to eliminate unwanted reactions to drugs.

The following types of antagonism are distinguished:

Direct functional antagonism

· indirect functional antagonism,

physical antagonism

· chemical antagonism.

Direct functional antagonism develops when drugs have opposite (multidirectional) effects on the same functional elements (receptors, enzymes, transport systems). A special case of direct antagonism is competitive antagonism. It occurs if drugs have a similar chemical structure and compete for communication with receptor.

Indirect functional antagonism develops in cases where drugs have an opposite effect on the functioning of an organ and, at the same time, their actions are based on different mechanisms.

Physical antagonism occurs as a result of the physical interaction of drugs: adsorption of one drug on the surface of another, resulting in the formation of inactive or poorly absorbed

Chemical antagonism occurs as a result of a chemical reaction between substances, which results in the formation of inactive compounds or complexes. Antagonists that act in this way are called antidotes.

When prescribing drugs in combination, you should ensure that there is no antagonism between them. The simultaneous prescription of several drugs (polypharmacy) can lead to changes in the rate of onset of the pharmacological effect, its severity and duration.

Having a clear understanding of the types of drug interactions, the pharmacist can give the following recommendations to prevent undesirable consequences for the patient of combined medications:

- take medications not simultaneously, but at intervals of 30–40–60 minutes;

- replace one of the medications with another;

- change the dosage regimen (dose and interval between administrations) of drugs;

Discontinue one of the drugs (if the first three steps do not eliminate the negative consequences of the interaction of the prescribed combination of drugs).

With the combined use of medicinal substances, their effect may be enhanced (synergism) or weakened (antagonism).

Synergy(from Greek syn- together, erg- work) - the unidirectional action of two or more medicinal substances, in which a pharmacological effect develops that exceeds the effects of each substance separately. Synergism of medicinal substances occurs in two forms: summation and potentiation of effects.

If the effect of the combined use of medicinal substances is equal to the sum of the effects of the individual substances included in the combination, the effect is determined as summation , or additive action . Summation occurs when medicinal substances that affect the same substrates (receptors, cells, etc.) are introduced into the body. For example, the vasoconstrictor and hypertensive effects of norepinephrine and phenylephrine, which stimulate a-adrenergic receptors in peripheral vessels, are summarized; the effects of inhalation anesthesia agents are summarized.

If one substance significantly enhances the pharmacological effect of another, this interaction is called potentiation . With potentiation, the total effect of the combination of two substances exceeds the sum of these effects. For example, chlorpromazine (an antipsychotic drug) potentiates the effect of anesthesia, which makes it possible to reduce the concentration of the latter.

Drugs can act on the same substrate ( direct synergy ) or have different localization of action ( indirect synergy ).

The phenomenon of synergy is often used in medical practice, as it allows one to obtain the desired pharmacological effect by prescribing several drugs in smaller doses. At the same time, the risk of increased side effects is reduced.

Antagonism(from Greek anti- against. agon– fight) – reduction or complete elimination of the pharmacological effect of one medicinal substance by another when used together. The phenomenon of antagonism is used in the treatment of poisoning and to eliminate unwanted reactions to drugs.

The following types of antagonism are distinguished: direct functional antagonism, indirect functional antagonism, physical antagonism, chemical antagonism.

Direct functional antagonism develops when medicinal substances have opposite (multidirectional) effects on the same functional elements (receptors, enzymes, transport systems, etc.). For example, functional antagonists include stimulants and blockers of b-adrenoreceptors, stimulants and blockers of M-cholinergic receptors. A special case of direct antagonism - competitive antagonism. It occurs when drugs have similar chemical structures and compete for binding to the receptor. Thus, naloxone is used as a competitive antagonist of morphine and other narcotic analgesics.

Some medicinal substances have a similar chemical structure to metabolites of microorganisms or tumor cells and compete with them for participation in one of the stages of the biochemical process. Such substances are called antimetabolites . By replacing one of the elements of the chain of biochemical reactions, antimetabolites disrupt the reproduction of microorganisms and tumor cells. For example, sulfonamides are competitive antagonists of para-aminobenzoic acid, which is necessary for the development of certain microorganisms, and methotrexate is a competitive antagonist of dihydrofolate reductase in tumor cells.

Indirect functional antagonism develops in cases where medicinal substances have opposite effects on the functioning of any organ and, at the same time, their action is based on different mechanisms. For example, indirect antagonists with respect to the effect on smooth muscle organs include aceclidine (increases the tone of smooth muscle organs by stimulating m-cholinergic receptors) and papaverine (reduces the tone of smooth muscle organs due to a direct myotropic effect).

Physical antagonism occurs as a result of the physical interaction of medicinal substances: the adsorption of one medicinal substance on the surface of another, resulting in the formation of inactive or poorly absorbed complexes (for example, the adsorption of medicinal substances and toxins on the surface of activated carbon). The phenomenon of physical antagonism is used in the treatment of poisoning.

Chemical antagonism occurs as a result of a chemical reaction between substances, as a result of which inactive compounds or complexes are formed. Antagonists that act in this way are called antidotes . For example, in case of poisoning with compounds of arsenic, mercury, and lead, sodium thiosulfate is used, as a result of a chemical reaction with which non-toxic sulfates are formed. In case of overdose or poisoning with cardiac glycosides, dimercaprol is used, which forms inactive complex compounds with them. In case of an overdose of heparin, prothiamine sulfate is administered, the cationic groups of which bind to the anionic centers of heparin, neutralizing its anticoagulant effect.

If, as a result of the combined use of drugs, a more pronounced therapeutic effect is achieved, negative reactions are weakened or prevented, such a combination of drugs is considered rational and therapeutically appropriate. For example, to prevent the neurotoxic effect of isoniazid, vitamin B6 is prescribed, to prevent candidiasis as a complication during treatment with broad-spectrum antibiotics - nystatin or levorin, to eliminate hypokalemia during treatment with saluretics - potassium chloride.

If, as a result of the simultaneous use of several drugs, the therapeutic effect is weakened, prevented or distorted, or undesirable effects develop, such combinations are considered irrational and therapeutically inappropriate ( drug incompatibility ).