Antagonism (biology): characteristics and types. Co-administration of drugs Antagonism Pharmacology Examples Chemical Pharmacological Physiological

Animals, plants, and micro-organisms have something in common - it's the will to survive. Therefore, many types of interactions between living organisms are antagonistic in nature. Find out what this means and what types of antagonism exist.

What is Antagonism?

Do you have an annoying little brother who antagonizes you? If not, then just imagine a similar situation. What does your brother or sister do to annoy you? He/she is probably making your life more difficult. This is not too far from the concept of antagonism, since it is associated with natural selection and.

Since organisms themselves are concentrated sources of energy and nutrients, they can become objects of antagonistic relationships. While antagonism is usually seen as an association between various types, it can also occur between members of the same species through competition and cannibalism.

Types of antagonism

There are different types of antagonism. Let's look at some of them:

Predation

An excellent example of predation is a pack of wolves chasing a deer. Deer are just one big food source. Wolves eat deer and get nutrients that keep them alive. If the deer hides from the wolves, it may be able to breed and pass on to the next generation. In the event that wolves overtake a deer, they get food and a chance to pass on their genes instead.

Competition

Competition is a negative relationship between organisms that need the same ones. For example, plants (even of the same species) growing in a small area can compete for sunlight or minerals in the soil. Some plants will be able to eradicate others in order to survive and reproduce, while others will die out.

Cannibalism

Another type of antagonism is cannibalism, where one animal eats another animal of its own kind. For some species, cannibalism is an extremely rare practice that is used in extreme survival situations, such as a mother mouse eating her young to avoid starvation.

Other examples of antagonism

Antagonistic interactions may also include defensive strategies using chemical and physical deterrents. Many plant species are capable of producing chemical substances into the soil to prevent the growth of other plants or protect against insects and grazing animals.

Plants and animals have developed physical adaptations such as hard shells (skin) and spines to thwart herbivore attacks. In addition, some species have adaptations that make them similar to others. Such adaptations can be used for both attack and defense.

Reverse agonism is the initiation of an overt cellular response by inhibition of spontaneous receptor activation.

Molecular response for reverse agonism can be:
inactivation of the activated receptor;
stabilization of the receptor in an inactive conformation.

This model looks like RR and I+RIR, where R is the activated state, I is the inverse agonist.

Antagonism is to prevent the action of the agonist. Many drugs bind to the receptor to form a drug-β complex that does not elicit a cellular response. Moreover, occupation of the receptor by the antagonist prevents either the binding of the agonist or the elicitation of a cellular response when the agonist binds to the receptor. Thus, antagonism may be the result of various molecular mechanisms. A mathematical description of the effects of various types of antagonists is given below. Briefly - antagonism can occur due to:

Bindings antagonist in the same receptor site normally occupied by an agonist. Antagonist binding prevents the agonist from occupying the center (competitive antagonism);

Bindings antagonist with a receptor site that is not normally occupied by an agonist (allosteric center), leading to conformational changes in the agonist binding center, which either prevents agonist binding or makes it impossible for a molecular response to occur.

Antagonist that binds to the allosteric center only in the absence of an agonist is called a non-competitive antagonist. If an antagonist can bind to an allosteric center even in the presence of a bound agonist, it is called a non-competitive antagonist. In this case, the center is often referred to as a ligand-binding center (where the ligand can be an agonist, antagonist, partial agonist, etc.).

Binding Antagonist may be reversible or irreversible. There are at least six possible types of antagonism. The effects exhibited by the antagonist in response to the action of the agonist are described in detail below.

Physiological antagonism different from pharmacological antagonism. Often the term "physiological (or functional) antagonism" is used incorrectly. This term describes the ability of an agonist (more often than an antagonist) to inhibit the response to another agonist by activating different, physically separated receptors. This can occur if two agonist receptors share the same cellular response components but act differently on them, or are linked by different cellular response components that elicit opposite tissue responses.

visual example is the interaction between norepinephrine and acetylcholine in arterioles. Norepinephrine causes contraction and acetylcholine causes relaxation. Of course, it is meaningless to describe norepinephrine as an acetylcholine antagonist, since acetylcholine can also be regarded as a norepinephrine antagonist, so the terms "agonist" and "antagonist" become interchangeable and do not make sense. The term "antagonist" is best used to describe drugs that inhibit the molecular response to an agonist. The term "functional antagonist" is best avoided.

Antagonism (from the Greek. antagonizoma, - I fight, compete) - the interaction of LP, in which there is a complete elimination or weakening

pharmacological effect one drug to another. The antagonism of two or more drugs is realized through the functional (physiological) systems of the body, therefore, pharmacological antagonism is called functional or physiological antagonism. Distinguish between direct and indirect antagonism.

Direct functional (competitive) antagonism develops when drugs act on the same cells or their receptors, but in the opposite direction (pharmacological incompatibility). As direct functional antagonists, the stimulant of M-cholinergic receptors aceclidin and the blocker of these receptors atropine, alpha-1-adrenergic agonist mezaton and alpha-1-blocker prazosin act.

Indirect functional antagonism occurs when drugs act antagonistically on various receptor structures. For example, beta-2-agonists (salbutamol, fenoterol) act as indirect functional antagonists in bronchial asthma. Bronchospasm is caused by the allergic mediator histamine as a result of its interaction with H-g histamine receptors. Salbutamol and fenoterol have an oroncho-expanding effect, but not through a direct effect on histamine receptors, but through other receptor systems - beta2-adrenergic receptors. Pharmacological incompatibility has found its application in practical medicine. Direct antagonism is widely used to correct adverse reactions, in the treatment of poisoning with drugs and poisons. For example, in case of carbachol poisoning as a result of stimulation of myocardial M-cholinergic receptors, bradycardia occurs (threat of cardiac arrest), and due to excitation of M-cholinergic receptors of the smooth muscles of the bronchi, bronchospasm occurs (threat of asphyxia). Direct functional antagonists in this case will be the M-cholinergic blocker atropine, which eliminates bradycardia and bronchospasm.

Preparations of hormones of the adrenal cortex and their synthetic analogues. Classification. Pharmacodynamics of mineral and glucocorticoids. Indications for appointment. Complications of corticosteroid therapy.

Preparations of hormones of the adrenal cortex.

Classification:

1. Glucocorticoids (Hydrocortisone, Corticosterone)

Hydrocortisone; synthetic drug: Prednisolone

2. Mineralcorticoids (Aldosterone, 11-Desoxycorticosterone)

Desoxycorticosterone acetate;

3. Sex hormones (Androsterone, Estrone)

Glucocorticoids act intracellularly. They interact with specific receptors in the cytoplasm of cells. In this case, the receptor is “activated”, which leads to its conformational changes. The resulting "steroid + receptor" complex penetrates the cell nucleus and, by binding to DNA, regulates the transcription of certain genes. This stimulates the formation of specific mRNAs that affect the synthesis of proteins and enzymes.

Glucocorticoids (hydrocortisone, etc.) have a pronounced and diverse effect on metabolism. On the part of carbohydrate metabolism, this is manifested by an increase in blood sugar, which is associated with more intense gluconeogenesis in the liver. Possible glycosuria.

Utilization of amino acids for gluconeogenesis leads to inhibition of protein synthesis with its catabolism preserved or somewhat accelerated (negative nitrogen balance occurs). This is one of the reasons for the delay in regenerative processes (in addition, cell proliferation and fibroblast function are suppressed). In children, the formation of tissues (including bone) is disrupted, growth slows down.

The effect on fat metabolism is manifested by the redistribution of fat. With the systematic use of glucocorticoids, significant amounts of fat accumulate on the face (moon face), dorsal part of the neck, and shoulders.

Typical changes water-salt metabolism. Glucocorticoids have mineralocorticoid activity: they retain sodium ions in the body (their reabsorption in the renal tubules increases) and increase the excretion (secretion) of potassium ions. In connection with the retention of sodium ions, the volume of plasma, the hydrophilicity of tissues increase, and blood pressure rises. More calcium ions are excreted (especially with an increased content in the body). Possible osteoporosis.

Glucocorticoids have anti-inflammatory and immunosuppressive effects.

Indications for use: sharp and chronic insufficiency adrenal glands. However, they are most widely used as anti-inflammatory and antiallergic agents. Due to these properties, glucocorticoids are successfully used in collagenoses, rheumatism, inflammatory diseases skin (eczema, etc.), allergic conditions (for example, with bronchial asthma, hay fever), some eye diseases (iritis, keratitis). They are also prescribed in the treatment of acute leukemia. Often in medical practice glucocorticoids are used in shock.

Side effects: retention in the tissues of excess amounts of water, development of edema, increased blood pressure. There may be a significant increase in blood sugar, a violation of the distribution of fat. The regeneration process slows down, ulceration of the mucous membrane is possible gastrointestinal tract, osteoporosis. Decreased resistance to infections. Featured mental disorders, violations menstrual cycle and other unwanted effects.

The ability of one in-va to one degree or another ↓ the effect of another is called antagonism.

distinguish direct and indirect antagonism.

The so-called synergoantagonism is distinguished, in which some effects of the combined substances are weakened, while others are weakened. Against the background of the action of α-blockers, the stimulating effect of adrenaline on α-Adrenoreceptors of vessels decreases, and on β-AR it becomes more pronounced.

Competitive antagonism– Drugs compete with agonists for the same specific receptors. Receptor blockade caused by a competitive antagonist can be eliminated by high doses of an agonist (drug or natural mediator)

Noncompetitive antagonism– The drug occupies other parts of the macromolecule that are not related to a specific receptor.

Antagonism-opposite effect of drugs joint application the effect of any drug from the combination is reduced. Very often used to warn or exclude side effects drugs or for drug and non-drug poisoning.

Possible variants of antagonism are:

a ) physico-chemical antagonism- the interaction of drugs occurs at the level of physical or chemical interaction and can occur independently of a living organism. An example of the physical interaction of drugs is the process of adsorption of large molecular toxins that have entered the stomach on molecules activated carbon, together with which they are then excreted from the body. An example of a chemical interaction is treatment with weak acid solutions in case of alkali poisoning or, conversely, with weak alkali solutions in case of acid poisoning (neutralization reaction).

b) physiological- this variant of antagonism can occur only in the body as a result of the effects of drugs on certain functions. There are the following variants of physiological antagonism:

According to the point of application, there are:

- direct antagonism- two substances act oppositely on the same system, on the same receptor, site of action. Example: the effect on the tone of intestinal smooth muscles of pilocarpine (M-cholinomimetic) and atropine (M-cholinergic blocker).

- indirect antagonism- two substances have opposite effects due to the impact on different points of application, different receptors, different body systems. Example: the effect on the rhythm of heart contractions of adrenaline (adrenomimetic) and atropine (anticholinergic).

According to the direction of action, there are:

- bilateral(competitive) antagonism, based on the competitive relationship of drugs for the same point of application. The drugs mutually cancel each other's effects with an increase in the concentration of any of them near the point of application. This principle works sulfa drugs, which exert their antibacterial effect due to competitive antagonism with para-aminobenzoic acid, which is necessary for the microbe to synthesize the cell wall.

- unilateral antagonism: one of the drugs has a stronger effect, therefore it is able to remove and prevent the action of the second, but not vice versa. Atropine is a pilocarpine antagonist, but pilocarpine is not an atropine antagonist.

By expression, they distinguish:

- full antagonism, when all the effects of one drug are removed or prevented by another.

- partial antagonism, when a drug removes or prevents only part of the effects of another drug. For example, the narcotic analgesic morphine, in addition to a strong analgesic effect, has a spasmodic effect on smooth muscles, which can lead to a sharp narrowing of the bile and urinary tract. To prevent this effect, along with morphine, atropine is administered, which does not affect the analgesic effect of morphine, but prevents its spasmodic effect.

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Synergism (from the Greek. synergos- acting together) - 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 may be based on pharmacokinetic and pharmacodynamic mechanisms, which will be discussed below.

Synergism can relate to both desired (therapeutic) and undesirable effects of drugs. So, for example, the combined administration of the thiazide diuretic dichlothiazide and the angiotensin-converting enzyme inhibitor enalapril leads to an increase in the hypotensive effect of each of the agents, and this combination is successfully used in the treatment hypertension. On the contrary, the simultaneous administration of aminoglycoside antibiotics (gentamicin) and loop diuretic furosemide causes a sharp increase in the risk of ototoxicity and the development of deafness.

Weakening effects medicines when they are used together, they are called antagonism. There are several types of antagonism:

Chemical antagonism or antidotism - chemical interaction substances with each other to form inactive products. For example, a chemical antagonist of iron ions is deferoxamine, which binds them into inactive complexes. Protamine sulfate (a molecule that has an excess positive charge) is a chemical antagonist of heparin (a molecule that has an excess negative charge). Protamine forms inactive complexes with heparin in the blood. Chemical antagonism underlies the action of antidotes (antidotes).

Pharmacological (direct) antagonism - antagonism caused by multidirectional action 2 medicinal substances on the same receptors in tissues. Pharmacological antagonism can be competitive (reversible) and non-competitive (irreversible). Let's consider them in a little more detail:

[Competitive antagonism. The competitive antagonist binds reversibly to the active site of the receptor, i.e. shields it from the action of the agonist. From the course of biochemistry it is known that the degree of binding of a substance to the receptor is proportional to the concentration of this substance. Therefore, the action 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 is required for the agonist to interact with the receptor. This situation is shown in Figure 9A. It is easy to see that the 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, it is necessary to keep the level sufficiently high at all times during treatment with competitive antagonists. In other words, clinical effect competitive antagonist will depend on its elimination half-life and the concentration of the full agonist.

[Noncompetitive antagonism. A non-competitive antagonist binds almost irreversibly to the active center of the receptor or interacts with its allosteric center altogether. Therefore, no matter how the concentration of the agonist increases, it is not able to displace the antagonist from its connection with the receptor. Since the part of the receptors that is associated with a non-competitive antagonist is no longer able to be activated, the value of E max decreases. In contrast, the affinity of the receptor for the agonist does not change, so the EC 50 value remains the same. On the dose-response curve, the action of a non-competitive antagonist appears as a compression of the curve about the vertical axis without shifting it to the right.

Non-competitive antagonists are rarely used in medical practice. On the one hand, they have an undeniable advantage, because. their action 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 drug occurs, it will be extremely difficult to eliminate its effect.

Table 2. Comparative characteristics of competitive and non-competitive antagonists

Losartan is a competitive antagonist for angiotensin AT 1 receptors, it disrupts the interaction of angiotensin II with receptors and helps to lower blood pressure. The effect of losartan can be overcome if a high dose of angiotensin II is administered. Valsartan is a non-competitive antagonist for the same AT 1 receptors. Its action cannot be overcome even with the introduction high doses angiotensin II.

Of interest is the interaction that takes place between full and partial receptor agonists. If the concentration of a full agonist exceeds the level of a partial agonist, then a maximum response is observed in the tissue. If the level of the partial agonist begins to rise, it displaces the full agonist from its 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 will occupy all the receptors). This situation is shown in Figure 9C.

Physiological (indirect) antagonism - antagonism associated with the influence of 2 drugs on different 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, which increases the transport of glucose into the cell and lowers the level of glycemia. Adrenaline activates b 2 -adrenergic receptors of the liver, 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 rendering emergency care patients with an overdose of insulin, which led to hypoglycemic coma.