Pharmacodynamic interactions of drugs
Pharmacodynamic interaction is considered to be a drug interaction, in which one of them can modify the pharmacological effect (as the main, and incidental) other.
Pharmacodynamic cooperation is in the field of direct action of drugs. The basis of this kind of interaction are also biochemical, and physico-chemical reactions, that occur in the organism on a membrane and subcellular levels, but are not between themselves medicinal substances, and between substances and functional cell systems.
Pharmacodynamics - one of the fundamental areas of Pharmacology, studied changes, occurring in the organism under the influence of drugs. In other words pharmacodynamics studies localization, mechanism of drug interactions in the body and the pharmacological effects, due to this process.
Thus, therapeutic effect of drugs is mediated in the body by their interaction with cell membranes, or other structures, having certain biochemical properties, which are commonly referred to as receptors, as well as other special cellular and extracellular biological substrates, or due to chemical interaction with endogenous compounds (antacids; substances, forming complexes - chelates).
Direct interaction with the substrate is most often carried out by reacting the drug with specific receptors, which can be any macromolecule or functionally important fragments thereof. In addition to specific receptors emit so-called non-specific receptors, when linked to drug substances which do not cause functional changes.
Most specific receptor proteins refers to cell, or localized in the cell membrane (holinoretseptory, insulin receptors and others.), or in the cytoplasm (the majority of steroid hormone receptors). There are specific receptors and different chemical nature, e.g. nuclear nucleic acid, which interact with antineoplastic agents from among alkylating agents. The active sites of acetylcholinesterase, monoamine oxidase and other enzymes are also contemplated as specific receptors. In particular, H-cholinergic receptors in isolated skeletal muscle isolated form, and established their detailed structure. The nature of many specific receptors not installed, although their existence is proved by different methodological techniques.
Specific receptors have a specific localization. For Example, M-cholinergic receptors located in postsynaptic membranes of cells in the effective area of the termination of cholinergic fibers, opioid receptors in the central nervous system are neurons of the gray matter.
The subject is also a study of the pharmacodynamics kinds of action of drugs. There are local, resorptive and reflex action, main and side, direct and indirect, Reversible and irreversible, selective and non-selective, therapeutic and toxic effects.
Depending on the functional role of cell interaction of substances can be local or generalized. Given the place of application and absorption into the blood, or distinguish local resorptive effect of drugs. In turn resorptive effect may be due to direct or indirect effect on the effector. For Example, drug can dilate blood vessels, acting on vascular smooth muscle (direct action) or acting on the cold receptors (indirect effect). Reflex action is an option of indirect. Its mechanism is the interaction of matter with the sensory nerve endings; emerging momentum relevant reflex arcs transferred to effector organs. So, eg, are annoying, expectorants and other substances.
The main (primary) referred to as the effect of substances, which is used for therapeutic purposes in each case, (in other cases it may be a side-). Action, has no therapeutic value in any particular case,, called side. Side effect, usually, unfavorable for the patient.
Most drugs act reversibly, but possibly irreversible action, such as the blockade of acetylcholinesterase.
Medicinal substances alter various body functions with varying degrees of selective.
Election (selective) the influence of drugs have rarely. By selectively include drugs, which preferentially affect some process in the body, eg, selectively ingibiruюt ferment COG-2 and, Consequently, suppress inflammation (meloxicam) or interact with specific receptor systems (eg, b1-blocker - acebutolol, блокатор a1A-adrenoreceptorov - tamsulosin; leykotrienovыh antagonist D4-receptor - montelukast sodium and others.). The essence of it is determined by the structures of biochemical properties of receptors.
Most drugs exhibits relative selectivity. For Example, atropine sulfate inhibits the action of acetylcholine on exocrine glands and smooth muscle, but it does not change its action on skeletal muscle. Non-absolute specificity of drugs can be explained by their ability to respond to the different structures of receptors, including nonspecific. The drugs, It has no direct impact on the well-defined receptors (dynamic cell structures, which have certain biochemical properties and are under continuous cell control), called nonspecific. The structure of such substances do not appear pharmacophore radicals, and their greater activity correlates with the size of the molecule, solubility in nonpolar solvents, etc.. d. Many of the non-specific active ingredients, salts of heavy metals e.g., inhibit the function of every living cell. They relate to the means of action obschekletochnogo (protoplazmatichyeskim unnamed).
Action of the substances in excess of their therapeutic doses called toxic. Adverse effects used by women during pregnancy drugs against the fetus is designated as fetotoxic effects. If such action leads to congenital malformations, his designated as teratogenic. Fetotoxic, and including teratogenic effects are usually considered as a manifestation of the side effects of drugs.
Pharmacodynamics of drugs depends on many factors, in particular by the properties of the substances, their dosages, the time of their appointment, combination with other drugs, as well as the characteristics of the organism, to which these substances act.
The most important factor, determining the effect of drugs, is their chemical structure. In general, substances with a similar chemical structure characterized by similar features and pharmacodynamics. However, in some cases pharmacodynamics of substances with very similar chemical structure may vary considerably. Examples are significant differences in the magnitude between stereoisomers pharmacological effects of some drugs (epinephrine, norepinephrine, propranolol, and others.). Setting values for the pharmacodynamics of drugs can have their physical and physicochemical properties: solubility in water and lipids, volatility, the degree of dissociation, purity, etc..
Actions of drugs largely depends on their concentration or dose. In general, the dose is increased, and increases the severity of the pharmacological effects of drugs. Most often, when it registered S-shaped relationship between dose and effect size; also possible linear and hyperbolic dependence. In comparing the activity of two drugs compare them isoefficiency dose, generally doses 50% effect (MATERIALS50). It is believed, A substance as many times as active compound B, how many ED50 A less substance ED50 compound B. Besides, distinguish the concept of "effectiveness" of substances. The effectiveness is judged by the magnitude of the maximal effect of the drug.
Pharmacodynamics of drugs can vary in repeated their appointment. So, may develop addiction to drugs. In order to achieve the same effect you need to increase the dose. During repeated administration of drugs to them may develop drug dependence.
The pharmacodynamics of drugs, as well as their pharmacokinetics, can be influenced by gender, age, functional and pathologic conditions, and genetic characteristics of the organism. Some substances have a therapeutic effect only in terms of pathology, such as antipyretics, antidepressants etc.. Genetic features (genetically determined enzimopaty) explain the idiosyncrasy, t. it is. unusual reactions to certain drugs. An example of idiosyncrasy may be significant lengthening of action of suxamethonium chloride (pseudocholinesterase deficiency), hemolysis when using primaquine (nedostatochnosty glucose-6-fosfatdegidrogenazы) and etc.
In addition to these factors closely linked to the pharmacodynamics pharmacokinetic characteristics of drugs, t. it is. their distribution, deposition, the nature of metabolism and excretion from the body.
