Implementation of pharmacotherapy. Modern standards of pharmacotherapy for stable angina pectoris

The use of drugs, which began with the emergence of medicine, throughout almost its entire history (up to the 20th century) was empirical in nature. The prerequisites for the formation of the scientific foundations of pharmacotherapy appeared only in the 19th century. in connection with the emergence of experimental pharmacology and the development of a functional direction in clinical research, as well as thanks to the successes of microbiology and chemistry, which became the basis for the birth of chemotherapy. In the 20th century scientific and technological progress has qualitatively changed the development of medical sciences, including pharmacology, determined the creation and production of new pharmacological preparations on an unprecedented scale, diverse in their spectrum of action and severity of influence on various functions of the body, as well as on the dynamics of pathological processes. At the same time, clinical disciplines turned to an extensive arsenal of technical tools for functional and laboratory diagnostics, which made it possible to objectively assess and monitor the effects of drugs in a clinical setting. At this stage, the development of clinical pharmacology contributed to the progress of pharmacotherapy (see. Pharmacology clinical), one of the founders of which in our country was B.E. Votchal.

The scientific principles of modern pharmacotherapy are formed on the basis of pharmacology data on the interaction of drugs with the body, primarily on their pharmacodynamics and pharmacokinetics, the features of which clinical pharmacology studies in a sick person, data from various medical sciences that reveal the pathological physiology and biochemical (biophysical) essence of the processes that make up the pathogenesis of the disease, as well as data from clinical disciplines that study the reflection of these processes on the symptoms of the disease, the dynamics of which can be a criterion for clinical evaluation the quality and degree of the pharmacological effect achieved.

The tactics of using the drug is substantiated by data on the mechanism of its action, bioavailability (absorption), distribution in tissues and elimination from the body.

For a limited number of drugs used, the pharmacological effect is a non-specific result of physical or chemical properties drug (for example, osmotic diuresis with the use of mannitol, the elimination of acidosis with the introduction of sodium bicarbonate), direct chemical interaction of the drug with any substance (for example, chelating excess copper in hepatocerebral dystrophy) or inclusion of a part of the chemical structure of the drug into a biomolecule (for example, synthesis of methylnoradrenaline when methyldopa is introduced into the body). For the vast majority of drugs, the nature of the pharmacological effect is considered within the framework of the receptor theory, which assumes a more or less selective interaction of the drug molecule with biomolecules (most often with enzymes on biological membranes) that perform a specific function in metabolism or regulation of certain activities. The probability of interaction is greater, the higher the concentration of the drug in the environment of its interaction with receptors. The concentration that provides the pharmacological effect sufficient to realize the therapeutic effect corresponds to the therapeutic concentration. If the required pharmacological effect due to interaction with receptors is expected within one organ (brain, heart, kidneys, etc.), then this organ can be considered as a target of drug action.

The concentration of the drug in the zone of its reaction with receptors, as well as its distribution in the body and excretion depend on the dose of the drug, its bioavailability with the chosen route of administration into the body (i.e., the ability to penetrate on the way to the site of action through various barriers - walls gastrointestinal tract, blood capillaries, interstitial media, cell membranes, etc.), on the characteristics of transport, the ability to bind to plasma proteins and undergo metabolism. The transport of drugs through various barriers can be passive (along the concentration gradient of a substance) and active (with the expenditure of energy for the transfer of drug molecules through membranes). Passively transported are most fat-soluble drugs that easily penetrate the lipid layer of cell membranes, as well as non-electrolytes and non-ionized molecules of acids and bases. The distribution of the drug in the body depends on the permeability of the histohematic barriers for it and the so-called volume of distribution (see. Pharmacokinetics). For drugs that are almost completely bound to plasma proteins (digitoxin, butadione, etc.), the volume of distribution is almost equal to the volume of plasma, and only a small part of the total amount of the administered drug enters the tissues. With the combined use of drugs that compete for binding to plasma proteins, it is possible to displace one drug from this connection by another and the molecules of the released drug pass into tissues, which may cause an increase in the pharmacological effect and toxic effect.

The main site of drug metabolism is the liver cells, and excretion is carried out mainly by the kidneys (by filtration in the glomerulus and active excretion by the tubular epithelium) and through the gastrointestinal tract. in liver cells medicines undergo enzymatic oxidation or reduction with the formation of metabolites, many of which subsequently form practically devoid of biological activity compounds with glucuronic, sulfuric and acetic acids, glycine, which are rapidly excreted by the kidneys.

Maintaining a stable concentration of the drug in the areas of its interaction with receptors (usually related to its concentration in blood plasma) is ensured by the introduction of the drug into the body at the same rate as its elimination. The latter slows down in diseases of the liver and kidneys. Known drugs that induce the activity of liver microsomal enzymes and thereby accelerate their own metabolism (meprotan, sibazon, etc.) and the metabolism of other drugs (phenobarbital, progesterone, etc.), as well as metabolic suppressors (etaperazine, chloramphenicol, PASK, etc. ). Their combined use with other drugs can change the rate of elimination of the latter.

In different individuals, the same doses of drugs often cause pharmacological effects that are different in degree, and sometimes in quality, which emphasizes the role of the body's reactivity in the formation of these effects. To characterize the reactions of the body to a drug, such concepts as drug sensitivity are used, which are characterized by threshold doses of the drug that cause initial reactions, as well as resistance, or resistance, to the drug - a significant decrease or absence of a pharmacological effect when using the maximum allowable dose.

The development of pharmacotherapy is characterized by its improvement in relation to certain nosological forms (for example, antirheumatic pharmacotherapy), pathological processes (pharmacotherapy of inflammation, dystrophy, etc.), as well as syndromes (for example, antishock, decongestant pharmacotherapy), which corresponds to the task of treating diseases, not a specific patient. This is reflected in the pharmacological classifications medicines, in particular, according to their nosological focus (for example, anti-tuberculosis drugs), pathogenetic, anti-syndromic or symptomatic action (for example, anti-inflammatory, anti-Parkinsonian, antitussive drugs), including also the designation of a number of drug groups according to their clinically most significant pharmacological effect (for example, cardiotonic drugs, diuretics , expectorants, etc.). This direction in the development of pharmacotherapy has certain advantages, primarily due to the possibility of a generalized formulation of its urgent problems and the use of experimental models to solve them. This does not exclude, however, the need to develop the foundations for the individualization of pharmacotherapy in its practical application in a particular patient.

Basic principles and elements of pharmacotherapy tactics. Most of the principles of pharmacotherapy coincide with the principles of therapy in general, the main ones include the principles of safety (treatment should not be more dangerous than the disease), rationality, controllability and individualization.

The requirement for the safety of treatment is especially relevant for modern pharmacotherapy, which is carried out with highly active drugs that are often pluripotent in relation to various functions of the body and not always predictable long-term consequences of their use. Therefore, the first of the questions that arise when prescribing treatment is the question of the very need to interfere with the medicine in the course of the disease. After establishing such a need, the prescription of a drug is possible if the probability of its therapeutic effect exceeds the probability of undesirable consequences of its use.

Reasonable doubts about the safety of the use of any drug (see. Side effects of drugs) define the strategic principle of treatment, which can be formulated as the principle of minimizing pharmacotherapy. It involves limiting the amount of pharmacotherapy in the total complex of patient treatment only by the amount and duration of the use of drugs, without which treatment is either impossible (not effective enough), or requires the use of more "dangerous" than pharmacotherapy, treatment methods. The provision of this principle is facilitated by a correct assessment of the possibilities of at least partial replacement of pharmacotherapy with such non-drug methods of liver treatment as physiotherapy , balneotherapy , climatotherapy , psychotherapy , reflexology and etc.

The principle of rationality implies that the optimal ratio of efficacy and safety of pharmacotherapy, due to which the maximum possible therapeutic effect of drugs is ensured with the lowest risk of their undesirable effects. The principle of rationality underlies the construction of pharmacotherapy tactics in a specific clinical situation, the analysis of which makes it possible to justify the choice of the most appropriate drug (combination of drugs), dosage form, dose and route of administration of the drug into the body, as well as the prediction of the duration of pharmacotherapy. The latter is determined taking into account not only the expected dynamics of the disease, but also the expected dynamics of the pharmacological effect and the possibility of the formation of various types drug addiction. With indications for the combined use of several drugs, the principle of rationality involves a medical assessment of the comparative significance of these indications in order to limit the number of prescribed drugs (the principle of economical pharmacotherapy). Thus, the possibility of etiotropic therapy or the appointment of agents that interrupt the pathogenesis of the underlying pathological process (inflammation, allergic reaction, etc.) can in some cases eliminate or minimize the need for the use of symptomatic agents or drugs acting on secondary links of pathogenesis.

Pharmacotherapy must be controlled. This principle provides for continuous medical analysis and assessment of both expected and unforeseen results of the use of the drug, which allows timely correction of the chosen treatment tactics by changing the dose and methods of drug administration, replacing an ineffective drug that caused side effects with another, etc. Ensuring this principle is based on the use of objective criteria and methods for assessing the quality and degree of therapeutic effect, as well as early detection of unwanted and side effects medicines. In accordance with this principle, the use of drugs should be avoided, the effect of which cannot be assessed in the expected time frame due to the lack of clear criteria for achieving it.

The principle of individualization of pharmacotherapy is not yet feasible in all cases, therefore, the intensive development of scientific prerequisites for its approval is one of the main features. modern approach to drug treatment. Accounting for individual differences in the action of drugs depending on the patient's condition and the characteristics of the pathogenesis of the disease gives, according to B.E. Watchala (1965), the basis for combating the biggest drawback of pharmacotherapy - the template. This is also facilitated by the disclosure of patterns that determine the variability of the pharmacokinetics of a drug depending on the genetic characteristics of individuals (see. Pharmacogenetics), the age of the patient, as well as the form of pathology and the specific conditions for the use of the drug (phase of the pathological process, the interaction of combined drugs, etc.). The practical implementation of the principle of individualization characterizes the highest level of possession of the method of pharmacotherapy, it is determined by the breadth of clinical thinking, the high level of general therapeutic qualification of the doctor and also depends on the completeness of information about the interaction of the drug with the patient's body.

In accordance with the principles outlined, the main elements of the tactics of rational pharmacotherapy in a particular patient include determining indications for pharmacotherapy, choosing a drug, ways and means of its administration, determining the dose, choosing criteria and means of controlling pharmacotherapy, and justifying its cancellation.

Indications for pharmacotherapy are determined based on the general principles of treatment of this form of pathology, which the doctor considers in accordance with the established diagnosis illness and possible complications, estimating it forecast, the degree of dysfunction, the presence of manifestations of the disease, bringing suffering to the patient. Pharmacotherapy is not indicated if the disease is not painful for the patient and its predicted outcome does not depend on the use of drugs, as well as in cases where non-drug methods of treatment are no less successful, being safe, or have advantages or even inevitable (for example, the need for emergency surgical operations).

If there are indications for pharmacotherapy, the latter is specified by the goals, the achievement of which is supposed to be ensured by the use of the drug, based on the knowledge of its pharmacodynamics. Also evaluated possible contraindications to pharmacotherapy, among which at this stage there may be an ambiguity in the diagnosis (for example, contraindications to the use of analgesics for acute abdomen) and incompatibilities between drug and non-drug treatments, e.g. defibrillation for cardiac arrhythmia after prior use cardiac glycosides. Sometimes, the ambiguity of the diagnosis, on the contrary, may be an indication for pharmacotherapy for ex juvantibus diagnosis. In some cases, indications for the use of drugs are determined by the results of trial treatment.

Sources of errors in evaluating indications for pharmacotherapy may be the lack of awareness of the doctor about the comparative therapeutic value of different methods of treatment, incorrect prognosis, but most often the inaccuracy and incompleteness of the diagnosis of the disease. For example, a relatively high frequency of unjustified use of sulfonamides and antibiotics in viral respiratory diseases is due to errors in the etiological diagnosis.

In the process of determining the scope of pharmacotherapy, indications for complex pharmacotherapy are substantiated, i.e. the use of drugs for different purposes and the use of combinations of drugs to achieve one of the goals of pharmacotherapy. Indications for complex pharmacotherapy may be the presence of two or more different pathological processes in a patient (due to complications or concomitant diseases), each of which requires drug treatment (for example, the development of pulmonary embolism in a patient with circulatory failure against the background of active rheumatism), or features of the course of the disease, requiring the simultaneous conduct of both etiological and pathogenetic and (and) symptomatic pharmacotherapy.

The purpose of a combination of drugs may be to enhance the therapeutic effect (with insufficient effectiveness of one drug) or increase its likelihood (with an incomplete etiological or pathogenetic diagnosis in a seriously ill patient), reduce the dose of a toxic or undesirable drug, as well as neutralize the undesirable effect of the main drug. Strengthening the therapeutic effect, as well as reducing the dose of the drug, is achieved by a combination of synergists of potentiating or additive action of drugs that complement the spectrum pharmacological action, as well as a combination of the main drug with a drug that increases its pharmacological effect. Rational are, for example, a combination of reserpine and dihydralazine to obtain a hypotensive effect: potassium preparations with glucose and insulin to eliminate hypokalemia, etc. Neutralization of the undesirable effect of the main drug is achieved by combining it with antagonists for an undesirable effect or with agents that compensate for the disturbances caused. For this purpose, they combine, for example, nitroglycerin with menthol (antagonism in the effect on cerebral vessels with possible synergism in the antianginal effect), saluretics with potassium-sparing diuretics and potassium preparations, etc.

Errors in the selection of combinations of drugs and their combinations within the framework of complex pharmacotherapy are most often due to insufficient awareness of the doctor about drug incompatibility, which is especially common when prescribing medicinal "cocktails" for intravenous infusions and when selecting combinations to neutralize the undesirable effects of a drug without taking into account the possibility of reducing their therapeutic effect (as, for example, when prescribing alkalis to eliminate side effects salicylates).

Choice of medicines or their combination is one of the most critical and difficult elements of pharmacotherapy. It includes a comparison of the features of action, pharmacokinetics, toxicity and other properties of drugs of the same type with the peculiarities of the pathogenesis of the disease and its manifestations in this patient (taking into account his general condition, the presence of concomitant diseases, the urgency of the situation), as well as the compatibility of drugs, if necessary, their combination and other data about both the drug and the patient. So, when indications for prescribing cardiac glycosides for myocardial insufficiency, the doctor cannot consider such drugs as corglicon, strophanthin, celanide, digoxin, digitoxin to be equivalent for choice only because the target cardiotonic effect is equally achievable when using any of them (in equivalent doses). For example, for long-term use, only intravenously administered drugs (Korglycon, Strofantin) cannot be selected from the listed drugs, and the most adequate ones for this clinical situation are selected from those used orally. If the patient has aortic valve insufficiency, celanide has the advantage, which, with the same cardiotonic effect, reduces the pulse to a lesser extent than digoxin and cigitoxin. The latter drugs have advantages in the tachysystolic form of atrial fibrillation, t . to. they inhibit atrioventricular conduction to a greater extent. Related kidney failure prevents the choice of digoxin (the drug is excreted mainly in the urine), and liver disease - digitoxin (the drug is mainly metabolized). With the simultaneous use of cardiac glycosides with drugs that bind plasma proteins (for example, sulfonamides), take into account the competitive ability for such a connection in some glycosides (for example, digitoxin binds to plasma proteins by 97%) and its absence in others (for example, in strophanthin ). In an urgent situation, one of the important criteria for choosing a particular drug is the speed of onset of the effect. Thus, the maximum effect with intravenous administration of cardiac glycosides is achieved after the administration of corglycone after 30 min(starts in 5 min), strophanthin - after 40-60 min(beginning of action in 5-10 min), and digoxin only after 1 1/2 -3 h.

In the process of choosing drugs, the principle of "economical pharmacotherapy" is implemented, if possible. For example, in patients with elevated blood pressure and ischemic disease heart, manifested by angina pectoris and cardiac arrhythmias, instead of the combined use of antihypertensive, antianginal and antiarrhythmic drugs, in some cases it is enough to prescribe only one medicinal product from group b-adrenergic blockers (see. Adrenoblocking agents) to achieve all the required effects (hypotensive, antianginal, antiarrhythmic).

The more experience and higher qualifications of the doctor, the more successful is usually the choice of pharmacotherapy, however, the often arising need to use drugs before the completion of the examination of the patient with an incomplete diagnosis (for example, in the absence of data on the causative agent of acute pneumonia already established) objectively reduces the likelihood of choosing the optimal one for this case of the drug. Therefore, the final choice of the drug is sometimes forced in the course of treatment, and so that it is not only an accidental consequence of trial and error, the doctor must analyze the possible reasons for the ineffectiveness of previously prescribed drugs to rationalize the choice of a new one. For example, complete absence The effect of the use of erythromycin in a patient with acute pneumonia (if it is not due to a low dose or a decrease in the bioavailability of the drug) determines the choice of an antibiotic with a different spectrum of action and makes it illogical to choose a penicillin that has a similar spectrum of action.

The choice of routes and methods of drug administration. There are enteral (oral and rectal) and parenteral routes of drug administration. The latter include non-injection (sublingually, in the form of inhalation, application to the skin and mucous membranes) and injection (subcutaneously, intramuscularly, intravenously, intraarterially), including injections into the cavity (subarachnoid, intrapleurally, into the cavity of the joints, etc.), routes of administration. In this case, the methods of administration may vary. So, intravenously, the drug can be administered through a puncture needle and through a catheter, the administration can be fast (bolus), slow jet and slow drip, etc.

When choosing the route and method of administration, the degree of urgency of the necessary assistance, the state of the body systems that ensure the bioavailability of the drug (stomach and intestines for enteral dosage forms, peripheral circulation for drugs administered subcutaneously, etc.), as well as the characteristics of the disease, which determines the advantages of any dosage forms and methods of drug administration, including the need to create especially high concentrations of the drug in the blood or in the focus of the pathological process. In some cases, a combination of routes of drug administration is appropriate (for example, intravenous and endobronchial administration of an antibiotic for acute lung abscess).

When medicines are taken orally great importance has a relationship between their intake and the time of food intake, which, depending on the nature, can significantly affect the effect and pharmacokinetics of the drug in the body, changing the pH of the medium in the stomach and absorption of the drug, participating in the dilution of the drug and interacting with it up to inactivation. So, for example, when taking griseofulvin along with fatty foods, the absorption of the drug increases, when taking tetracycline with milk and other products containing Ca 2+, its bioavailability decreases. Most resorptive drugs should be taken between meals (60-30 min before meals), unless the conditions for a more rational relationship with the rhythm and nature of nutrition are specifically stipulated. Immediately before a meal, during or immediately after a meal, for example, enzyme preparations (gastric juice, pancreatic enzymes, etc.) are used.

Determination of the dose of the drug produced according to the route of administration. However, differences in dose can be quite significant. So, for example, the daily dose of sodium salt of benzylpenicillin with intralumbar administration to patients with purulent meningitis (2000-5000 IU) is much less than with intravenous and intramuscular injection drug (up to 50,000,000 units or more).

Determining the individual dose of the drug, proceed from the idea of its average dose, i.e. dose that provides therapeutic concentrations of the drug in the body with the chosen route of administration in most patients (in the so-called average patient): an individual dose is defined as a deviation from the average necessary in a particular case. The need to reduce the dose arises due to age-related characteristics or pathology of drug elimination systems, with hypoproteinemia, hypersensitivity or limitation of the number of receptors in target organs (for example, for cardiac glycosides in myocarditis), with individual hypersensitivity of the patient to this or similar in action drugs, which is often observed, for example, in relation to caffeine, benzodiazepine derivatives, etc. Higher-than-average doses may be needed when the bioavailability of the drug is reduced, the patient's low sensitivity to it, and also with the simultaneous use of drugs with competitive properties or accelerating the metabolism or excretion of this drug. The individual dose of a medicinal product may differ significantly from the average indicated in the formularies: for example, the individual dose of atropine that causes dry mouth varies from different persons from 2 to 100 drops of a 0.1% solution. If it exceeds the approved higher dose, the doctor must strictly justify the need and possibility of such an excess. In the process of using drugs, their dose is adjusted depending on the observed effect and may change with a change in the patient's condition and the total amount of pharmacotherapy.

Taking into account the purpose and depending on the duration of action of the administered drug, a single, daily, and sometimes course dose is determined. When determining a single dose, the criterion for its adequacy is the required therapeutic effect in the expected duration of the drug after its single administration. In some cases, the amount of the drug for a single use corresponds to a part of the known daily dose, divided into several single doses. To ensure the continuity of the effect of short-acting drugs (several hours), their daily dose is calculated based on the duration of the action of a single dose, which determines the intervals between drug administrations during the day. Doses of drugs that accumulate in the body or give a cumulative effect (see. Cumulation), may be different at the beginning of treatment (initial doses, loading doses) and throughout it (maintenance doses). For such drugs, various initial dosing schemes are being developed, providing for a different rate of onset of effect depending on the rate of saturation (for example, schemes for fast, medium and slow digitalization rates have been developed for digitalis cumulating cardiac glycosides). The maintenance daily dose is set in such cases after the achievement of a therapeutic effect, based on the amount of the drug accumulated by this time in the body and the coefficient of daily elimination of the drug. The course dose in most cases is determined by the dynamics of the pathological process under the influence of pharmacotherapy and the dynamics of the effectiveness of the drug used. A number of drugs are characterized by a decrease in the effect as they are used as a result of tachyphylaxis, acceleration of metabolism due to the induction of liver enzymes, the formation of antibodies to the drug, and for other reasons. For drugs that are highly toxic or capable of causing drug dependence, the course dose has regulated restrictions on the absolute amount of the drug used or on the permissible duration of its use.

Choice of criteria and means of drug action control necessary both to assess the therapeutic effect and to identify their undesirable effects. As criteria, the dynamics of the subjective sensations of the patient (for example, pain, itching, thirst, appetite, quality of sleep, etc.) and the dynamics of objective signs of the disease can be chosen. Since the subjective sensations of the patient can be very variable regardless of medication (not to mention the possibility of dissimilation, aggravation), objective criteria are preferable. Their search is also desirable in the case of the use of drugs, the effect of which is assessed mainly subjectively (for example, analgesics, antidepressants). It should be taken into account, in particular, that the disappearance of any symptom of the disease is usually accompanied by an expansion of the range of the patient's functional capabilities; this can be detected using certain objective tests (for example, an increase in the range of motion of the affected joint after taking an analgesic, a change in behavior and intellectual performance after the use of an antidepressant, etc.).

The criteria for the effect or undesirable action are only those changes in the patient's condition that can be put in a reasonable connection with the use of the drug. For example, a convincing indicator of the anticoagulant effect of heparin is the prolongation of blood clotting time.

Comparative value of clinical, instrumental and laboratory methods research as a means of objective control of pharmacotherapy is determined by the degree of specificity of the changes detected with their help for the action of a given drug. Methods that allow quantitative characterization of controlled changes have advantages, but only if they are no less specific. So, for example, the control of saturation with digoxin by dynamics clinical manifestations heart failure and ECG changes is more adequate and better contributes to the detection of digitalis intoxication than the dynamics of the concentration of the drug in the blood, which is expressed by quantitative parameters, but does not reflect the effect of digoxin on the myocardium.

Errors in evaluating the actions of a drug are most often associated with insufficient consideration of the fact that the identification of changes expected from its action does not in itself prove a causal relationship of these changes with the pharmacological effect of this drug. The dynamics of the observed symptom can also be determined by such reasons as a psychotherapeutic effect, similar to the effect placebo, an adjacent effect of another agent used simultaneously (for example, the disappearance of extrasystoles under the action of an antianginal, and not an antiarrhythmic, drug used simultaneously), as well as restoration of impaired functions not associated with treatment or regression of the pathological process due to the onset of recovery or remission of the disease. A correct assessment of the relationship between signs of improvement in the patient's condition and the action of drugs allows you to timely review the indications for individual drugs, cancel unnecessary ones (for example, if the related effect is sufficient) or replace them with more effective ones.

Rationale for discontinuation and discontinuation of medicinal products complete pharmacotherapy or some stage thereof. Continuation of pharmacotherapy after the patient's recovery is contraindicated. In the process of complex pharmacotherapy, the need to cancel a certain drug or a combination of them is justified by the achievement of the goal of pharmacotherapy, which is usually associated either with the completion of the pathological process (for etiotropic and pathogenetic treatment agents), or with the restoration or compensation of any function, the violation of which served as an indication for the appointment. of this drug. In addition, the rationale for drug withdrawal during therapy may be: a decrease or disappearance of the therapeutic effect due to the peculiarities of the pharmacological action of the drug or the formation of irreversible changes in target organs during the course of the disease; the predominance at some stage of therapy of contraindications over indications for prescribing the drug due to the dynamics of the pathological process or due to the increase in time of the risk of dangerous consequences of the use of the drug (a special case of such justification for cancellation is the completion of the course for drugs with a regulated course dose or duration of use); the manifestation of a toxic or side effect of the drug, excluding the possibility of replacing the drug (for example, digitalis intoxication is an absolute contraindication to the use of all cardiac glycosides).

Cancellation of the drug is absolutely contraindicated if it is the only means of maintaining vital functions - respiration, blood circulation, metabolism. A contraindication to the abolition of the drug may also be the decompensation of functions that ensure the adaptation of the patient to the environment, which is expected in connection with its abolition.

In some diseases, as well as congenital and acquired pathological conditions, there is a need for so-called maintenance pharmacotherapy for a long time, sometimes for life. This occurs in cases where the drug is used as a means of replacement pharmacotherapy (for example, insulin in diabetes mellitus), in the formation of a drug-dependent variant of the course of the disease with a threat lethal outcome due to drug withdrawal (for example, glucocorticoids in a hormone-dependent course bronchial asthma), as well as in the correction of stable functional disorders that significantly affect the patient's adaptation to environment and on the prognosis of the disease (for example, lifelong use of cardiac glycosides in patients with chronic heart failure due to heart disease).

With indications and no contraindications to drug withdrawal, the doctor determines the necessary rate of withdrawal, taking into account the fact that changes in the body caused by the drug can acquire pathogenic significance in the event of a simultaneous cessation of its administration - the so-called withdrawal syndrome. To the greatest extent, this applies to drugs that act at the level of regulatory systems with feedback structures (see. Functional systems), primarily to hormones and means of mediator action. So, for example, with the abolition of long-term use of glucocorticoids, the development of adrenal insufficiency is possible (due to a lack of adrenocorticotropic hormone); sudden withdrawal of clonidine in patients hypertension can cause severe hypertensive crises, etc. Possible withdrawal options include: stopping the administration of the drug, which is possible for the vast majority of drugs in the case of their short-term use; cancellation by gradually reducing the daily dose at the time necessary for the regression of functional changes associated with the pharmacological effect (for example, increased sensitivity of adrenergic receptors due to the use of sympatholytics or adrenoceptor blocking agents), or to restore a drug-suppressed function (for example, secretion of adrenocorticotropic hormone, suppressed by the introduction of glucocorticoids ); cancellation "under cover" of another pharmacological drug that prevents the development of undesirable effects of withdrawal (for example, the abolition of glucocorticoids against the background of the use of "hormone-sparing" anti-inflammatory, immunosuppressive or other drugs. Each of these options is chosen taking into account the prognosis of the so-called withdrawal syndrome based on specific data on pharmacodynamics the drug and the functional state of the systems involved in the manifestations of the pharmacological effect.

Features of pharmacotherapy in children and the elderly. Until the middle of the 20th century. features of pharmacotherapy were studied mainly in children, and only in the 60s. within the framework of age-related pharmacology, a geriatric direction has emerged.

Pharmacotherapy in children differs in a more complex approach to determining its tactics, tk. by the nature of the interaction with most drugs, the child's body approaches the adult body only by the age of 12-14. Differences in the state of the systems that react with the drug and determine its transport, metabolism, and excretion in different periods of the postnatal development of the child are so significant that they exclude any standardization in the tactics of pharmacotherapy in children without taking into account the degree of development of these systems for a given age period.

Most of all, the features of the interaction of the body with the drug are expressed in newborns and infants. For the bioavailability of drugs in enteral dosage forms during these periods, the abundance of circulatory and lymphatic vascularization of the stomach and intestines, low acidity of gastric juice (3-4 times lower than in adults), and high permeability of intestinal wall pores for large molecules are essential during these periods. In general, these features facilitate the passive transport of drugs, especially alkaloids (caffeine, etc.), while the bioavailability of drugs that require active transport is reduced in infants (for example, tetracycline, riboflavin, retinol are absorbed worse). The amount of albumin in the plasma of newborns and infants is less than in adults, while many drugs are less tightly bound to proteins and are more easily displaced by natural metabolites, such as bilirubin. This creates conditions for increased desorption (release from protein binding) of drugs bound by proteins (digoxin, sulfonamides, etc.), and an increase in the free fraction of the drug in the blood with a corresponding increase in action up to toxic, which is especially important to take into account in hyperbilirubinemia of newborns and with the combined use of drugs that are competitively bound by plasma proteins. Some drugs are more slowly removed from the blood, the younger the child. Thus, the half-life of sibazon from the blood in premature newborns is 2 times longer than in full-term ones, and 4 times longer than in children 4-8 years old.

The distribution of drugs in the body of a child occurs according to the same patterns as in an adult, but the penetration of most of them into various bodies, including the brain, in newborns and infants is higher than in older children, due to the incomplete development of histohematic barriers. This is due, in particular, to the increased intake of various fat-soluble drugs into the brain, incl. a number of sleeping pills, the inhibitory effect of which on the brain of newborns is more pronounced than in adults. At the same time, many of these drugs are sorbed by the brain tissue to a lesser extent; in newborns, it contains less lipids. Features of the kinetics of water-soluble drugs are determined by a large volume of extracellular water in the body of newborns and infants, as well as a high rate of extracellular water exchange (almost 4 times higher than in adults), which contributes to a faster elimination of drugs.

Metabolic inactivation of drugs in children is limited due to the smaller mass of the liver parenchyma, low activity of oxidative enzymes and the detoxification system through the formation of conjugates with glucuronic acid, which completes its development only by the age of 12. In newborns, qualitative differences were also established in the biotransformation of a number of drugs (for example, chlorpromazine, sibazon, promedol), characterized by the formation of metabolites not found in older children and adults. The abundance of exceptions to the patterns established in adults requires knowledge of the characteristics of the biotransformation of individual drugs. It is known, for example, that in newborns and infants, the metabolism of amidopyrine, butadione, sibazon, chloramphenicol, morphine and a number of other drugs is significantly slowed down. Sufficiently justified should be considered the position according to which in children the rate of metabolism of drugs, culminating in the formation of conjugates with sulfuric acid, does not differ significantly from that in adults, and for drugs inactivated as a result of the formation of conjugates with glucuronic acid, the slower the metabolism, the less child's age.

Excretion of drugs by the kidneys in newborns and children of the first year of life is generally slowed down both due to lower glomerular filtration than in adults (according to creatinine release - about 2 times) and lower permeability of the basement membrane of the renal glomeruli, and due to incomplete development of enzymes. systems that provide excretion in the tubules of the kidneys of drugs and their metabolites. Some drugs, such as benzylpenicillin, in children already at the age of 2-3 months. excreted at the same rate as in adults.

When choosing a drug, in addition to the features of its pharmacokinetics in children, the features of its pharmacodynamics are also taken into account, which depend on the level of development of systems that determine the implementation of the pharmacological effect at a given age of the child. For example, the hypotensive effect of ganglioblockers in children of the first two years of life is weak, in infants the hypertensive effect of ephedrine is weakened with a pronounced effect on blood pressure of mezaton, etc. The therapeutic significance of the expected pharmacological effect is correlated with the risk of adverse drug effects, the likelihood and nature of which are not the same in children of different ages and in adults. So, for example, compared with older children in children of the first 3 months. life, the likelihood of developing hemolysis and methemoglobinemia due to the use of nitrofurans, vikasol and other drugs is much higher, due to the high content of fetal hemoglobin in their blood. The probability of toxic effects of drugs in equivalent (per unit body weight) doses in newborns and infants is lower for some drugs (adrenaline, strychnine), for others it is higher (morphine, chloramphenicol, tetracycline, etc.). Taking into account the undesirable effects of drugs, I.V. Markov and V.I. Kalinicheva (1980) distinguish groups of drugs whose use in newborns is no more dangerous than in other age groups (penicillins, macrolides, nystatin, caffeine, phenobarbital, etc.); drugs used with caution (atropine, chlorpromazine, amidopyrine, cardiac glycosides, aminophylline, gentamicin, lincomycin); drugs contraindicated in newborns (levomycetin, tetracycline, kanamycin, monomycin, nalidixic acid, sulfonamides, salicylates, morphine and morphine-like analgesics).

Determination of the dose of the drug in children cannot be limited to the search for criteria for equivalence to the dose of an adult (by body weight, body surface, etc.), since the metabolism and excretion of drugs in. children may be qualitatively different from those of adults. The average doses of drugs are determined from the clinical experience of their use in different age groups of children. Based on this experience, general dosing patterns are established in units of mass (grams, milligrams), volume (drops, milliliters), activity per 1 kg body weight or 1 m 2 body surface or for 1 month or 1 year of a child's life for individual drugs (anaprilin, eufillin, etc.), and in more complex terms - in milligrams per 1 kg body weight for certain age periods (taking into account age-related changes in drug metabolism systems and the reactivity of the child's body).

The choice of effect criteria and means of drug action control in children in all age groups is limited mainly by objective signs of the dynamics of the pathological process, syndrome or symptom, because subjective criteria (informativeness of the patient's complaints) are much less valuable than in adults, and in children of the first year of life they are generally absent. The use of objective instrumental controls is also limited, requiring the active participation of the patient in the study (a certain posture, arbitrary delay or increase in breathing, etc.). All this makes it difficult to provide controlled pharmacotherapy, especially in young children. Accordingly, the importance of continuous clinical monitoring of the slightest deviations in the state of various functions and behavior of the child against the background of the use of the drug increases, especially in the expected periods of its pharmacological action.

Cancellation of drugs in children is carried out for the same reasons as in adults.

Pharmacotherapy in elderly and senile patients acquires features as the body undergoes changes in metabolism, barrier functions of tissues, metabolism and drug excretion systems, as well as the sensitivity to drugs of various organs and the reactivity of the body as a whole. Lack of caution in the choice and dosing of drugs for elderly patients is, apparently, one of the reasons for their greater frequency of side effects (according to various researchers, in people over 70 years of age, side effects of drugs are observed 3-7 times more often, than in patients 20-30 years old).

The bioavailability of drugs used enterally in the elderly is reduced due to a decrease in the secretory, motor and absorption functions of the gastrointestinal tract. The distribution of drugs is influenced by a decrease in the water content in the body and the amount of albumin in the blood, which is characteristic of elderly and senile people, a decrease in the mass of most organs, the number of functioning blood vessels and narrowing of their lumen, and a change in the permeability of histohematic barriers. The mass of the liver parenchyma in persons over 70 years of age is reduced, the antitoxic function of the liver is reduced, the activity of oxidative enzymes is weakened. This is associated with a slowdown in the metabolism of drugs, in particular those whose inactivation ends with the formation of sulfates. The rate of excretion of drugs by the kidneys also decreases due to a weakening of energy-dependent excretion through the epithelium of the tubules, a decrease in the number of functioning nephrons (in persons over 70 years of age, they become 30-50% less), a decrease in the efficiency of the renal plasma flow and glomerular filtration rate.

The tactics of pharmacotherapy in elderly and senile patients should include: limiting the choice of drugs with low toxicity: prescribing higher doses during the initial use of drugs in enteral dosage forms; reduction in the dose of drugs (especially when administered parenterally), excreted by the kidneys or slowly metabolized in the liver. Doses of certain drugs (neuroleptics, cardiotonic drugs, diuretics, etc.) recommended for the initial use of elderly and senile people average 1/2 dose of a middle-aged adult. However, these provisions do not apply to all drugs (for example, vitamins, many antibiotics and sulfonamides can be used in normal doses), therefore, in order to develop rational pharmacotherapy tactics, one should take into account the peculiarity of pharmacological effects, which in elderly and senile people is determined by changes in sensitivity to certain drugs and even qualitative changes in reactions to individual drugs.

In elderly and senile persons, regular features of reactions to drugs acting on the central nervous system have been established, which are associated, in particular, with an increase in aging of the body of dystrophic changes in neurons, with a decrease in the number of nerve cells and the number of axons, and also with a decrease in the functional activity of ts.n.s. It is shown that for the manifestation of an exciting effect on the c.n.s. phenamine, strychnine, ephedrine in the elderly, larger doses of these drugs are needed than in middle-aged people. To drugs that depress the central nervous system, in particular to barbiturates and other hypnotics. neuroleptics of different groups, including reserpine, narcotic analgesics, some benzodiazepine derivatives (chlosepid), etc., on the contrary, increased sensitivity is noted. The direct pharmacological effect of these drugs is achieved in smaller doses and is often combined with pronounced manifestations of undesirable effects (respiratory depression, muscle relaxation, excitation of the vomiting center), while the use of these drugs in doses that are therapeutic for middle-aged people often leads to intoxication. Thus, special care should be taken when using even low-toxic hypnotics and sedatives in the elderly (described, for example, bromide poisoning), especially neuroleptics.

In the elderly, more often than in other age groups, there is a need for the use of cardiotonic, antihypertensive and diuretic drugs. Clinical observations indicate an increased sensitivity of the myocardium of the elderly to the toxic effect of cardiac glycosides. This favors the choice of low cumulative drugs, the slow pace of initial digitalization and requires more frequent monitoring of the adequacy of the selected dose. When choosing antihypertensive drugs, consider increased danger a sharp decrease in blood pressure and protostatic collapse with the use of ganglionic blockers, sympatholytics, as well as an undesirable effect on the central nervous system. a number of drugs (reserpine, dehydralazine). Under the influence of saluretics, elderly people may experience a more pronounced loss of potassium (per unit volume of diuresis) with worse than middle-aged people tolerance of these losses and the ability to restore electrolyte balance. At the same time, hypersensitivity to the action of aldosterone antagonists is often noted, as a result of which they can be used at lower doses.

There are reasons to believe that the simultaneous use of vitamin complexes, in particular vitamins B 1 , B 6 , B 15, contributes to the increase in the effectiveness and reduction of undesirable consequences of pharmacotherapy in elderly and senile streets.

Features of pharmacotherapy in pregnant women and nursing mothers. Prevention of undesirable effects on the fetus and on the infant of drugs that cross the placenta or excreted with mother's milk is central to the tactics of pharmacotherapy in pregnant women and nursing mothers.

Features of pharmacotherapy in pregnant women are largely determined by the prognosis of the effect of the drug on the developing fetus. The placental barrier is permeable to varying degrees for the vast majority of drugs. Getting into the blood and tissues of the fetus, the drug can cause: pharmacological effect; embryotoxic effect, impaired fetal development, teratogenic effect.

The pharmacological effect in the fetus, depending on the dose of the drug, may differ significantly from that observed in a pregnant woman. Thus, the appointment of a pregnant woman with indirect anticoagulants in doses that cause a moderate decrease in prothrombin in her can cause multiple hemorrhages in the tissues of the fetus. The quantitative and qualitative features of the pharmacological effect in the fetal body are determined by the imperfect development of its systems that interact with drugs, the peculiarities of their distribution in tissues (for example, mezaton accumulates in the fetal brain 3 times more than in a pregnant woman), metabolism and excretion.

The embryotoxic effect is most characteristic of drugs that are inactivated by their metabolism, because enzyme activity of liver microsomes in the fetus is low. Imperfect metabolism explains the high toxicity to the fetus of chloramphenicol, morphine, short-acting barbiturates (hexenal, thiopental-sodium) with less toxicity of long-acting barbiturates (barbital, phenobarbital), which are excreted from the body mainly unchanged. A peculiar form of the unusual action of drugs that displace protein-bound bilirubin is the so-called jaundice of the cerebral nuclei. It is observed in the fetus when prescribed to pregnant women for a long time or in high doses of drugs bound by plasma proteins (sulfonamides, sibazon, hydrocortisone, etc.), and is explained by the weakness of the blood-brain barrier in the fetus and the weak bond of bilirubin with plasma protein.

The indirect effect of drugs on fetal development has different forms. These include, for example, fetal respiratory disorders due to a decrease in placental blood flow or hypoxemia when pregnant women use adrenomimetics that cause vasospasm, hemoglobin binders (nitrites), drugs that provoke at pregnant exacerbation of bronchial asthma ( acetylsalicylic acid and etc.); deficiency of B vitamins when using antibiotics, diuretics, laxatives; calcium deficiency when using tetracycline; hypercortisolism syndrome due to the displacement of cortisol by drugs bound by plasma proteins.

The teratogenic effect of drugs is most pronounced during the so-called critical periods of embryogenesis - the period of implantation (the first week after conception), the period of placentation (9-12 weeks) and especially during the period of organogenesis (3-6 weeks of pregnancy). From the second trimester of pregnancy, the likelihood of a teratogenic effect of drugs decreases, but is not completely excluded, because. subtle processes of functional differentiation of fetal tissues continue. It is believed that the teratogenic effect of some drugs is due to their ability to be included in the metabolism of the fetus due to the similarity of their chemical structure with natural metabolites (for example, the teratogenic activity of halidomide was associated with its similarity to riboflavin). In animal experiments, fetal abnormalities are caused by a large number of drugs, but since species differences have also been established, the value of experimental data for predicting teratogenic effects individual drugs a person is not high. Of the agents affecting the central nervous system, teratogenic activity was found, in addition to thalidomide, in phenothiazine derivatives (causing various developmental anomalies in animals and phocomelia in humans), reserpine, meprotan, chlosepide; experimentally established high teratogenic activity of some vitamin preparations, in particular retinol (cleavage of the palate in 100% of animals, anencephaly in 50%. possible microphthalmia, absence of the lens), nicotinic acid, as well as benzylpenicillin (syndactyly in 45% of animals), adrenocorticotropic hormone, cortisone , cytostatic agents.

Thus, taking into account the effect of drugs on the fetus, any pharmacotherapy in the first trimester of pregnancy has relative contraindications due to currently incomplete data on the teratogenic activity of drugs. In subsequent periods of pregnancy, there are contraindications to drugs with an embryotoxic effect and disrupting the normal development of the fetus, as well as to drugs that affect labor activity. Pharmacotherapy is carried out during this period only for serious indications, including the occurrence of diseases that in themselves disrupt the course of pregnancy and fetal development.

Most often, the need for the use of drugs in pregnant women arises in connection with infectious diseases, as well as phlebothrombosis, which often complicates the course of pregnancy, arterial hypertension, edema. When choosing drugs in these cases, their relative risk to the fetus during this period of pregnancy is taken into account.

Of the antibacterial agents in the first trimester of pregnancy, ampicillin, which does not have teratogenic activity, oxacillin, which poorly penetrates the placental barrier, a combination of these drugs (ampiox), and also cephalosporins. However, in high doses, these drugs, like sulfonamides, can cause the appearance of "jaundice of the cerebral nuclei" in the fetus. Erythromycin penetrates the placental barrier relatively poorly (concentrations in fetal plasma are 5 times less than in maternal plasma). In the first trimester of pregnancy, long-acting sulfonamides are contraindicated, because. they have teratogenic activity. In all periods of pregnancy, the use of tetracycline and levomycetin, which have a pronounced embryotoxic effect, should be excluded.

Of the anticoagulants, heparin is preferred, which does not pass through the placental barrier and is therefore harmless to the fetus. Indirect anticoagulants are contraindicated not only because of the risk of hemorrhages in the fetus, their use in the first trimester of pregnancy also threatens with developmental abnormalities.

Antihypertensive drugs and diuretics are often used for toxicosis of the second half of pregnancy, when a teratogenic effect is unlikely. It is preferable to administer methyldopa, less often octadine, in case of hypertensive crises intravenously - apressin (40-100 mg) and dichlothiazide (150-200 mg) in the form of single infusions (it should be remembered that prolonged use of dichlothiazide causes the development of hyperglycemia, hyperbilirubinemia, and thrombocytopenia in the fetus). Reserpine, whose biotransformation is slow even in a newborn, in daily dose for a pregnant woman more than 0.5 mg can cause hypersecretion in the nose and bronchi of the fetus and, as a result, obstruction respiratory tract. The use of ganglioblockers is avoided due to the threat of meconium ileus in the fetus.

Of the diuretics, furosemide has teratogenic activity, but in the second half of pregnancy, its use is practically not limited. When using dichlothiazide in pregnant women with preeclampsia, the possibility of an increase in the level of uric acid in the blood is taken into account.

Features of pharmacotherapy in nursing mothers are reduced to reduce the risk of undesirable effects of drugs taken by the mother on the infant. They enter the body of a child during feeding and may have a toxic effect on drugs used to wash the nipples, in particular solutions of boric acid (accumulate in the tissues of the child, lead to metabolic acidosis and kidney damage) and lead acetate (the threat of lead intoxication with the development of encephalopathy). Women using such solutions should thoroughly wash their nipples with water before feeding the baby.

The excretion of different drugs by the mammary gland is different; the concentration of some of them (for example, thiouracil) in breast milk can be several times higher than in the mother's blood plasma, which can cause both pharmacological effects and toxic effects on the child's body. Even a small amount of drugs that penetrate into breast milk, is not always safe both in terms of toxic effects (due to the imperfection of the metabolism of drugs in the body of an infant), and due to the possible sensitization of the child's body with the formation drug allergy. Lithium salts, thiouracil, nalidixic acid, amantadine, gold preparations, radioactive calcium and iodine preparations are contraindicated for nursing mothers. The lower the age of the infant, the more contraindicated is the treatment of the mother with isoniazid (impairs the absorption of vitamin B 6), chloramphenicol (toxic effect), tetracyclines (impaired development of the child's teeth, skeleton); sulfonamides, salicylates should be used with caution. If it is necessary to use these drugs by a nursing mother for a long time or in high doses, it is advisable to transfer the child to artificial feeding.

Bibliography: Votchal B.E. Sketches of clinical pharmacology, M., 1965; Zapadnyuk V.I. Geriatric pharmacology, Kiev, 1977; Markova I.V. and Kalinichev V.I. Pediatric pharmacology, L., 1980; Khmelevskaya S.S. Organization of drug care for the elderly and senile, Kiev, 1983.

1.3. Clinical pharmacokinetics (basic kinetic processes, concepts of bioavailability, distribution, absorption and elimination constants, therapeutic window, etc. Interaction of drugs and food)
If pharmacodynamic mechanisms can be studied in animal experiments or in vitro on isolated cell and tissue cultures, then

clinical pharmacokinetics- the second important

the most important section of clinical pharmacology, operating

relies on data obtained only with the participation of a person. This section studies, from a quantitative and qualitative side, the totality of all the processes of passage and transformation of a drug in a healthy and diseased organism and reveals patterns between the concentration of the drug and the observed effects. The main pharmacokinetic processes include:
A) Release of the drug from the dosage form
B) Absorption (absorption) C) Distribution D) Metabolism

D) Excretion (excretion)

Understanding these processes makes it possible to choose the optimal route of drug administration, dose the drug correctly, predict the rate of onset and severity of the pharmacodynamic effect, its duration, assess the likelihood of adverse events, especially toxic ones, and rationally compose drug combinations. The ability to use pharmacokinetic processes in practice is of particular importance when analyzing the failure of pharmacotherapy, as well as in the treatment of patients with severe functional disorders of the heart, liver, kidneys, etc. These processes are described by a number of quantitative parameters, the most significant of which are :
Area under the pharmacokinetic curve (AUC) "concentration-time" –
an integral parameter proportional to the total amount of drugs in the body. According to this indicator, one can judge both the maximum concentration of the drug in the blood, and the rate of its intake and excretion from the body.
Bioavailability (f) shows what part of the drug (%) when administered extravascularly reaches the systemic blood flow and the rate at which this process occurs.
Absolute bioavailability is defined as the ratio of the AUC of the drug administered by the study method (oral, intramuscularly) to the AUC when administered intravenously.
About relative bioavailability say when comparing two different dosage forms of the same drug.
General bioavailability reflects the part of the dose of the drug that, when taken orally, reached the systemic circulation, both unchanged and in the form of metabolites formed during the absorption process (“first pass effect”, first pass metabolism)
Absorption constant (Rab) – characterize-
is the rate of entry of drugs into the systemic circulation during extravascular administration.

Maximum concentration (Cmax) -

characterizes the efficacy and safety of the drug, its value should not go beyond the therapeutic range.

The time to reach the maximum con-

centration (Tmax) - with a linear dependence "concentration-effect" allows you to estimate the time of onset of the maximum effect of the drug. However, it should be noted that for some drugs, the peak pharmacological

General provisions

action may lag behind its recorded maximum concentration in time.

Volume of distribution (Vd) – conditional while-
indicator reflecting the degree of uptake of the drug by tissues from plasma or blood serum. Conventionally, this is the volume in which it is necessary to dissolve the entire dose of the drug that has entered the body in order to obtain a concentration equal to its plasma concentration.
Clearance (CL) - characterizes the rate of "purification" of the body from medicinal substance. This part of the apparent volume of distribution, which is released from the drug per unit of time. Allocate total, renal and extra-renal clearance, depending on the routes of elimination of the drug.

Elimination rate constant (Kel) –

characterizes the rate of processes leading to the removal of the drug from the body.

Half-life (T½)- proportional

nalene elimination constant (T½ = 0.603 Kel) and shows how long the concentration of the drug in the body is halved.

Pharmacokinetic processes are closely related to the observed pharmacodynamic effects of drugs. First of all, it concerns the increase in the severity of the pharmacological action of the drug with an increase in its dose. For most drugs, a fairly high linear correlation has been established between the level of the drug in the blood and the clinical manifestation of the effect. At the same time, this effect cannot increase indefinitely with a constant increase in concentration and is limited by a certain physiological limit. In practice, reference material should be used, which usually contains basic information on the rate of increase, severity and duration of the effect, depending on the dosing regimen of the drug. These parameters are established during clinical trials of drugs in a large number of patients. Obviously, the rate of development and the severity of the effect will be maximum with intravascular administration of the drug, an alternative to which can sometimes be sublingual administration. However, some drugs require mandatory primary passage through the liver, where they are converted into their active form (most ACE inhibitors)

Pathological changes in the bone-articular apparatus arose even in our distant ancestors. A modern medicine cites disappointing facts: more than half of the population of our country (over 65 years old) suffer from joint disease; one of them - arthrosis - does not affect only 3% of older people, the rest are faced with its manifestations. Rheumatoid polyarthritis after 5 years from the onset of its development leads to disability. main reason this phenomenon - the lack of adequate treatment, so it was developed international protocol treatment chronic diseases joints.

Pain as a constant companion of life

For almost every person diagnosed with polyarthritis, pain becomes a constant companion of life. Most often, pain is associated with the development of inflammation of the inner layer of the articular bag, which covers the surface of all elements that form the joint (including tendons), except for cartilage. The main functions of this layer are cartilage nutrition, cushioning and protection of the joint cavity from the penetration of infection into it.

Research shows a sad picture:

in 1/5 of all patients with polyarthritis, constant pain in intensity exceeds the average threshold;
the intensity of pain affects the life expectancy of older people more than the risk of developing life-threatening conditions.

Acute pain causes the development of functional inferiority of the joint already at early stages diseases. It plunges a person into a state of constant emotional stress, anxiety and even depression, which, in turn, leads to cardiovascular disorders. Therefore elimination pain syndrome- the primary task of the treatment of polyarthritis of any origin.

Official standards of pharmacotherapy

The first problem that the links in the chain of properly selected therapy are aimed at is the removal of pain. In traditional pharmacological practice, analgesics and non-steroidal anti-inflammatory drugs are used for this purpose.

First link: anti-inflammatory therapy

Inflammation of the joint occurs with the release of specific proteins (inflammatory mediators), which cause the breakdown of joint tissues and the appearance of common symptoms: fever, fatigue, weakness. NSAIDs inhibit the synthesis of these proteins and improve overall well-being. The following drugs are usually prescribed:

diclofenac;
indomethacin;
piroxicam;
ibuprofen.

But representatives of this group of drugs have a lot of side effects that cause the development of secondary pathologies against the background of the main treatment. So the following types of negative effects of these drugs on the patient's body have been established:

damage to the gastrointestinal tract, the ability to provoke the formation of erosion and bleeding;
damage to kidney tissue, causing the development of interstitial nephritis;
pronounced negative effect on cells and liver function;
the danger of use in patients with concomitant lung diseases, due to the ability to provoke bouts of bronchospasm;
slowing down the processes of restoration of the cartilaginous layer of the joint;
increase in blood pressure.

These side effects significantly reduce the quality of life of patients with polyarthritis. Therefore, pharmacologists directed their efforts to create a new generation of anti-inflammatory drugs and achieved good results.

New generation drugs (the so-called selective COX2 inhibitors) are able to suppress the synthesis of proteins that provoke inflammation not only in the joints, but also in other organs and tissues, in particular blood vessels. At the same time, they have a number of advantages over their predecessors:

much less likely to cause the development of secondary pathology on the part of the digestive system;
do not have a negative effect on the synthesis of new cells of the cartilage tissue of the joint;
do not destroy kidney tissue;
inhibit the formation of cells that destroy bone tissue, therefore, are especially effective in concomitant osteoporosis;
can be used in patients with arterial hypertension, as they do not significantly affect the increase in blood pressure numbers;
can be used for a long time as the main pharmaceutical agent in patients with deforming osteoarthritis with severe persistent pain syndrome.

However, many physicians stubbornly continue to treat polyarthritis with drugs from another group of NSAIDs, adhering to outdated standards of treatment. In addition, there are unfounded assumptions about the negative effect of selective COX 2 inhibitors on the state of cardio-vascular system and their ability to cause liver dysfunction. Recent research proves the inconsistency of such claims.

The main representatives of this group of drugs:

nimesulide;
meloxicam;
celebrex (celecoxib);
rofecoxib;
etodolac;
cimicoxib and other coxibs;
lornoxicam.

However, when taking even the most effective of these drugs, it is necessary to find the optimal dose, since small amounts lead to insufficient effect, and too large doses are toxic. Nimesulide (nise) is most effective at a daily dosage of 200 mg; Meloxicam - 15 mg, Celebrex - 100-400, an average of 200 mg.

Second link: analgesics

European and domestic rheumatologists adhere to the point of view that the main drug for the treatment of polyarthritis should be an anesthetic, and the course of taking NSAIDs should go by the wayside and be as short as possible. But taking into account the fact that polyarthritis is a long-term disease, which is accompanied by constant inflammation of the articular elements, many experts still bring non-steroidal anti-inflammatory drugs to the first place.

The most famous drugs used among analgesics are katadolon, reopyrin and butadione. The latter drug is also available in the form of an ointment, which allows it to be applied locally in the lesion.

Third link: chondroprotectors

Chondroprotectors are slow-acting drugs that allow you to control the processes that occur inside the joint with polyarthritis. They are based on one of the 2 main components of cartilage: glucosamine and chondroitin. There are drugs that include both of these components.

There is no fundamental difference in the effects of taking one of the above components, since they are closely related in the body: glucosamine stimulates the production of chondroitin, and chondroitin, breaking down, forms glucosamine. Both of these tools can not only slow down the decay of the cartilage layers of the joint, but also partially restore them. In addition, it has been proven that these drugs have analgesic and anti-inflammatory effects. The anti-inflammatory properties of chondroitin allow us to consider it as a promising drug for the treatment of diseases not associated with the musculoskeletal system.

The main drugs of this group:

teraflex (complex preparation);
chondroitin sulfate;
dona (monopreparation based on glucosamine);
artra.

All of them should be taken for a long time, since the first effect appears only after a month from the start of the intake.

Fourth link: muscle relaxants

These drugs eliminate reflex muscle spasms as one of the factors that provoke the development of pain. They increase the therapeutic activity of non-steroidal anti-inflammatory drugs by about 1/4.

The use of muscle relaxants helps to get the following effect:

reduce pain syndrome;
prevent the formation of contractures;
improve the function of the musculoskeletal system.

Mostly used relaxants of the central type of action: sirdalud, midokalm, baclofen, tranxen, diazepam. All of them have a wide range of side effects: cause drowsiness, muscle weakness, dry mouth, lower arterial pressure. Sirdalud and midokalm are considered the mildest preparations.

Folk remedies as an addition to the main treatment

Traditional medicine offers a wide variety of remedies for the treatment of polyarthritis. The most effective of them are the means of api- and phytotherapy.

Popular among patients with polyarthritis treatment with compresses or rubbing with various alcohol tinctures. It's really good way relieve pain and reduce inflammation somewhat, however, it must be remembered that effective pathogenetic treatment of polyarthritis ethnoscience still cannot offer. Therefore, its methods can only be used in conjunction with the traditional treatment regimen.

We should not forget that traditional medicine often uses products based on plant materials. And modern environmental conditions make one deeply doubt its quality and the safety of the active components.

Be sure to consult your doctor before treating diseases. This will help to take into account individual tolerance, confirm the diagnosis, make sure the treatment is correct and exclude negative drug interactions. If you use prescriptions without consulting a doctor, then this is entirely at your own risk. All information on the site is presented for informational purposes and is not a medical aid. You are solely responsible for the application.