Pharmacotherapy– an integral concept denoting a set of treatment methods based on the use of drugs.

The main principle of clinical pharmacotherapy- rationality. The choice of drugs should be minimal in terms of the number of names and doses and at the same time adequate to the severity of the disease in order to provide effective assistance to the suffering person.

Pharmacotherapy must be effective, i.e. ensure the successful solution of treatment objectives in certain clinical situations. The strategic goals of pharmacotherapy can be different: cure (in the traditional sense), slowing down the development or stopping an exacerbation, preventing the development of the disease (and its complications) or eliminating painful or prognostic unfavorable symptoms. In chronic diseases, medical science has determined that the main goal of treating patients is control of the disease with a good quality of life (i.e., the patient’s subjectively good condition, physical mobility, absence of pain and discomfort, ability to care for oneself, social activity).

The main task of pharmacotherapy- improving the quality of life of the patient. Quality of life is determined by the following criteria:

Physical mobility;

No pain or discomfort;

Ability to serve oneself;

Ability for normal social activity.

Prescription of medications cannot be carried out “just in case”, without specific indications.

Drug risks have become a major medical problem over the past 40 years. This concern intensified after the thalidomide disaster of 1960-61, when pregnant women took it and gave birth to children who horrified the world with their deformities. This was an exceptionally dramatic example from the entire practice of drug therapy.

The following types of pharmacotherapy are distinguished:

1. Etiotropic (elimination of the cause of the disease).

2. Pathogenetic (affecting the mechanism of disease development).

3. Replacement (compensation for the lack of vital substances in the body).

4. Symptomatic (elimination of individual syndromes or symptoms of the disease).

5. General strengthening (restoration of damaged parts of the body’s adaptation system).

6. Preventive (prevention of the development of an acute process or exacerbation of a chronic one).

In acute illness, treatment most often begins with etiotropic or pathogenetic pharmacotherapy. In case of exacerbation of chronic diseases, the choice of the type of pharmacotherapy depends on the nature, severity and localization of the pathological process, the age and gender of the patient, the state of his compensatory systems; in most cases, treatment includes all types of pharmacotherapy.

Before starting pharmacotherapy, the need for it should be determined.

If intervention during the course of the disease is necessary, the drug can be prescribed provided that the likelihood of its therapeutic effect is greater than the likelihood of undesirable consequences of its use.

Pharmacotherapy is not indicated if the disease does not change the patient’s quality of life, its predicted outcome does not depend on the use of drugs, and also if non-drug treatments are effective and safe, more preferable or inevitable (for example, the need for emergency surgery).

One of the most important principles of clinical pharmacology is to prescribe a drug when indicated.

Prescribing “just in case” B vitamins, which exhibit allergenic properties in some people, increases the number of anaphylactic reactions.

Fever is a protective reaction of the body, and in the vast majority of cases, at temperatures below 38 C, antipyretics are not required.

The routine prescription of antibiotics for viral diseases from the first day of illness for the “prevention of secondary infection” has become the talk of the town.

It has been proven that the number of bacterial complications in viral infections does not depend on the use of antibiotics, and in a retrospective analysis of cases of fatal antibiotic-induced AS, it was found that in 60% of cases there were no indications for their use.

In this case, it is worth paying attention to the reputation of the company that produces the medicines, since the same medicines produced by different companies may have serious qualitative differences.

№p/p	Subject	number of hours	lecture date
	Basics of pharmacotherapy. Pharmacotherapy is the science of using medicinal substances for therapeutic purposes. The following types of pharmacotherapy are distinguished: etiotropic, pathogenetic, symptomatic, replacement and preventive. Study of clinical pharmacotherapy, tasks. Study of clinical pharmacokinetics. Basic questions of pharmacodynamics. Relationship between pharmacokinetics and pharmacodynamics. Medicines in modern medicine. Clinical pharmacology in the 20th century. The influence of various factors on the effect of drugs. Mechanisms of action of drugs. Selectivity of drug action. Doses, tolerance, drug overdose. Drug interactions. Side effects of drugs. The role of the pharmacist in solving important problems of pharmacotherapy. Terminology.
	Diseases of the cardiovascular system. Pharmacotherapy of hypertension. Pharmacotherapy of heart failure. Pharmacotherapy of coronary heart disease. Pharmacotherapy of stenacordia, heart rhythm disturbances. Selection of drugs, dosage regimen. Methods for assessing effectiveness and safety. Diagnosis, correction and prevention of adverse drug reactions. Possible interactions when combined with drugs from other groups.

Topic 1. Basics of pharmacotherapy

Target: know the methodology of the subject.

Plan:

The concept of pharmacotherapy as a science.

Types of pharmacotherapy.

Basic concepts and terms of pharmacotherapy.

The tasks and significance of pharmacotherapy in medicine and pharmacy.

Ways of introducing drugs into the body.

Types of action of drugs

Compatibility of drugs.

Features of pharmacotherapy in children and the elderly.

Pharmacotherapy in elderly and senile people.

Features of pharmacotherapy in pregnant women and nursing mothers.

Pharmacotherapy - a branch of pharmacology that studies patient therapy with drugs.

Depending on the characteristics of the impact on the pathological process, the following types of pharmacotherapy are distinguished:

Etiotropic therapy is aimed at eliminating the cause (etiology) of the disease or reducing the effect of the causative factor of the disease, for example, the use of antimicrobial drugs for infectious diseases or antidotes (antidotes) for poisoning with toxic substances. This type of therapy is the most effective.

Pathogenetic therapy - the effect of drugs aimed at eliminating or suppressing the mechanisms of disease development. Most pharmacotherapeutic agents belong to pathogenetic drugs. For example, the use of antihypertensive, antiarrhythmic, anti-inflammatory, psychotropic and other drugs.

Symptomatic therapy is aimed at eliminating or reducing individual symptoms of the disease, eliminating or limiting individual manifestations of the disease. The use of drugs that do not affect the cause or mechanism of the disease. Medicines that eliminate individual manifestations of the disease are called symptomatic drugs. Their therapeutic effect is based only on the weakening of some symptom of the disease.

For example, the use of painkillers for headaches, the use of laxatives for constipation or astringents for diarrhea, acetylsalicylic acid for colds.

Replacement therapy used when there is a deficiency in the patient’s body of biologically active substances (hormones, enzymes, vitamins, etc.), the introduction of which, without eliminating the cause of the disease, ensures a normal life for a person for many years (type I diabetes, hypothyroidism, anemia associated with iron deficiency , deficiency of vitamin B2 and folic acid, chronic adrenal insufficiency, etc.).

Preventative therapy carried out to prevent diseases. The group of preventive agents includes some antiviral, disinfectant drugs, vaccines, serums, etc.

Currently, in connection with the practical needs of life, a new direction is being formed - pharmacology (valeology is the science of health), designed to improve people's health with the help of medicines with adaptogenic and antioxidant effects.

Pharmacotherapy strategy comes down to eliminating or reducing the effect of the causes that cause diseases, eliminating or suppressing the mechanisms of disease development, on the one hand, as well as stimulating natural protective mechanisms of compensation and recovery, on the other.

The fastest and most complete recovery is achieved with the simultaneous use of drugs that suppress the cause of the disease and the mechanisms of its development (pathogenesis), and drugs that strengthen the body’s defense mechanisms, so the doctor sometimes justifiably strives to simultaneously prescribe several drugs (polypharmacy).

The effectiveness of pharmacotherapy increases when it is carried out in combination with a certain regimen of rest or activity, an appropriate diet, and suitable physiotherapeutic procedures. It can be an addition to surgical treatment methods.

In carrying out rational individual pharmacotherapy based on knowledge of pharmacokinetics, drug metabolism, pharmacogenetics and pharmacodynamics, the pharmacist provides significant assistance to the doctor.

Clinical pharmacology is a science that studies the effects of drugs on the body of a sick person.

Her tasks:

1) testing new pharmacological agents;

2) development of methods for the most effective and safe use of drugs;

3) clinical trials and re-evaluation of old drugs;

4) information support and advisory assistance to medical workers.

Resolves issues such as:

1) selection of a drug for the treatment of a particular patient;

3) determining the route of administration of the medicinal substance;

5) prevention and elimination of adverse reactions of the medicinal substance.

In addition to the theoretical problems developed by clinical pharmacology, in practice it solves a number of other issues:

1) selection of medications for the treatment of a particular patient;

2) determination of the most rational dosage forms and mode of their use;

3) determination of routes of administration of the medicinal substance;

4) monitoring the effect of the drug;

5) prevention and elimination of adverse reactions and undesirable consequences of drug interactions.

Pharmacology is a medical and biological science about the effects of drugs on living organisms, the fate of drugs in the body, and the principles of creating new drugs. The word "pharmacology" comes from the Greek words pharmacon - medicine and logos - teaching, word. Thus, the literal translation: pharmacology is the science of medicines, drug science. Modern medicine is divided into pharmacy and pharmacology. Pharmaceutical sciences (pharmaceutical chemistry, pharmacognosy, pharmaceutical technology) study the physicochemical properties of medicines, medicinal raw materials of plant and animal origin, and the technology of manufacturing medicines in factories and pharmacies. Pharmacology studies changes in the body that occur under the influence of drugs (pharmacodynamics), as well as their absorption, distribution, biotransformation and excretion (pharmacokinetics). The mechanism of action of drugs is considered as an influence on biological systems of varying complexity - from the whole organism to individual cells, subcellular formations and cytoreceptors.

Medicine- is one or more substances used for the treatment and prevention of diseases. Dosage form is an easy-to-use form of drug release (solid, liquid, soft, extraction and maximally purified).

An important information characteristic of medicines is their international nonproprietary names (INN). They, identifying the active pharmaceutical substance (about 8,000 in the world), ensure communication and exchange of information between health care professionals and scientists from different countries, are in the public domain and are assigned by the World Health Organization (WHO). Commercial trade names are given to ready-made single- or multi-component drugs produced in a specific dose and dosage form. Trade names are the property of the manufacturer. In Russia

Only a small number of domestic drugs that have traditional national names have been preserved in the drug nomenclature.

The Russian “List of Vital and Essential Medicines” includes medicines, without the use of which life-threatening diseases and syndromes progress, their course worsens, complications appear, the patient’s death may occur, as well as medicines for the treatment of socially significant diseases. The list is regularly reviewed and updated.

Each stage of the life cycle of a medicinal product is subject to a standard of “good practice” (Good Practice) or code of professional practice. Standards guarantee the effectiveness, safety and pharmaceutical aspects of the quality of finished products, protect the interests of consumers and facilitate international trade by recognizing the results of work carried out in one country by other countries (Table 1).

Preclinical pharmacological studies are carried out on laboratory animals (intact and with models of human diseases), in culture of cells and their organelles. These studies must provide evidence and reliability of the data while respecting the principles of humane treatment of laboratory animals. The following experimental methods are used:

screening (English) to screen - sift) - standard methods for assessing the activity of chemical compounds in comparison with the effect of known drugs (the effectiveness of screening is low - on average, for one drug brought to the stage of clinical trials, there are 5 - 10 thousand pre-tested compounds);

in-depth study of the mechanism of action using physiological, biochemical, biophysical, morphohistochemical, electron microscopic methods, and molecular biology methods;

pharmacokinetics study;

determination of acute and chronic toxicity;

identification of specific types of toxicity (immunotoxic, allergenic, mutagenic, carcinogenic, embryotoxic, teratogenic, fetotoxic effects, the ability to cause drug dependence).

Clinical pharmacology studies the effects of drugs on the body of a sick person - pharmacodynamics and pharmacokinetics in a clinical setting. The tasks of clinical pharmacology are clinical trials of new drugs, re-evaluation of known drugs, development of methods for the effective and safe use of drugs, elimination of undesirable consequences of their interactions, conducting pharmacokinetic studies, organizing an information service.

Table1. Good Pharmaceutical Practice Standards

Stage of the drug life cycle	Standard
Preclinical studies	Rules for preclinical studies of the safety and effectiveness of medicines { Good Laboratory Practice, GLP)
Clinical trials	Good clinical practice including planning, conducting, completing, verifying, reviewing, and reporting clinical trial results (Good Clinical Practice, GCP)
Production	Rules for organizing production and quality control of medicines (Good ManufacturinG Practice, GMP)
Wholesale trade	Wholesale trade rules (Good Distribution Practice, GDP)
Retail trade and pharmacies	Rules of pharmaceutical (pharmacy) practice (Good Pharmacy Practice, GPP)

Clinical trials of new drugs of phases I - IV (Table 2) are carried out in comparison with the effect of reference drugs of a given pharmacological group or placebo. Placebo (lat. placebo - I like it) is a dosage form that does not contain a drug, has the same appearance, smell, taste as the real drug. The placebo effect is especially important in internal diseases with emotional disorders (arterial hypertension, angina, bronchial asthma, peptic ulcer), neurosis, mental disorders, pain syndromes.

Patients in the experimental and control groups should be the same in age, form and stage of the disease, and initial background treatment. Groups are formed by random distribution of patients (randomization).

Table 2. Clinical trial phases

	Based on the results of preclinical studies of efficacy and safety, the effect of the drug is studied in various doses in healthy volunteers (5 - 10 people) to assess the tolerability of the drug; determine pharmacokinetic parameters for single and repeated doses, interaction with food
	The effectiveness and safety of a drug in comparative terms (placebo, reference drug) are studied in a limited number of patients (100 - 200) with the disease for which the drug is intended to treat; determine the range of its therapeutic doses
	A comparative study of the drug in established therapeutic doses and specific dosage forms is carried out in a large number of patients of different ages, including patients with concomitant diseases of the cardiovascular system, kidneys and liver; interactions with other drugs are identified and pharmacoeconomic aspects are assessed. Based on the results of this phase of testing, a decision is made to register the drug
	The phase begins during the registration of the drug and continues after its appearance on the market. Its tasks: solving additional questions regarding the use of the drug, expanding the indications for its use, acquiring experience for doctors in its use, positioning the drug on the pharmaceutical market
Post-registration surveillance (phase V)	Collection and analysis of reports of side effects of a drug, preparation of reviews on its safety based on studying the use of the drug in tens of thousands of patients, analysis of the effect on survival

During clinical trials, open, “single-blind” and “double-blind” methods are used. At "just a blind man" In this method, the patient is not told whether he has taken the test drug, the reference drug, or placebo. The doctor and the person requesting the study know this. At "double blind" In this method, neither the patient nor the attending physician has information. Only the person requesting the study is informed about how the clinical experiment is conducted. Clinical, instrumental, laboratory and morphological methods are used.

The scientific value of the results obtained during clinical trials should not conflict with ethical standards aimed at protecting the health and rights of patients. Patients are included in a clinical trial only subject to their voluntary informed consent and on the basis of a positive conclusion from an independent ethical committee.

The development of a new drug is an extremely expensive, complex and time-consuming process. Only one out of 10,000 investigational substances reaches registration and becomes a drug. The duration of collecting data on the drug being created reaches 8 - 12 years.

In addition to their beneficial therapeutic effects, many drugs can cause unwanted reactions, in some cases leading to severe complications and even death.

Adverse reactions and complications are possible when taking any medications.

Modern medicine has achieved great success in the prevention and treatment of various diseases, largely due to the availability of highly effective drugs. However, over the past half century, the number of complications from medications has increased dramatically. Their frequency in outpatient treatment reaches 10-20%, and 0.5-5% of patients require treatment.

The reasons for this are the not always justified rapid introduction of drugs into medical practice, the widespread use of polytherapy (polypharmacy), i.e. the simultaneous prescription of a large number of drugs, and, finally, self-medication.

The following types of side effects and complications of pharmacotherapy are distinguished:

1) side effects associated with the pharmacological activity of drugs;

2) toxic complications, regardless of dose;

3) secondary effects associated with a violation of the immunobiological properties of the body (decreased immunity, dysbacteriosis, candidomycosis, etc.);

4) allergic reactions;

5) withdrawal syndrome that occurs when you stop taking a drug.

Side effects of drugs associated with their pharmacological activity can occur both with an overdose of drugs and when they are used in therapeutic doses.

Drug overdose can be absolute (too large a dose is taken) and relative (the dose is therapeutic, but the concentration in the blood and cells is too high, due to the characteristics of the pharmacokinetics of the drug in a given patient). In case of overdose, there is a significant increase in the main and toxic effects of the drugs. For example, an overdose of vasodilators causes collapse, stimulants - convulsions, hypnotics - anesthesia, etc.

Complications when using the drug in normal therapeutic doses, not associated with overdose, do not occur in all patients and, as a rule, with long-term use. For example, tricyclic antidepressants (amitriptyline, etc.), in addition to the main effect on the central nervous system, cause dry mouth, constipation, accommodation disorders, etc.

Toxic complications, regardless of the dose, in some cases cannot be avoided at all for some drugs. For example, cytostatics not only suppress the growth of tumor cells, but also inhibit the bone marrow and damage all rapidly dividing cells.

Violation of the immunobiological properties of the body is possible when using highly active antibiotics and other antimicrobial agents that cause changes in the normal bacterial microflora (superinfection, dysbacteriosis, candidomycosis).

The side effects of drugs depend on the nature of the underlying disease. Systemic lupus erythematosus is often accompanied by steroid-induced arterial hypertension.

Allergic reactions are the most common complication of drug therapy. Allergic reactions are caused by the interaction of an antigen with an antibody and are not related to the dose of drugs. There are two types of immunopathological reactions that can be caused by drugs: 1) immediate type reaction (urticaria, bronchospasm, anaphylactic shock, rash, Quincke's edema, serum sickness, anaphylactoid reaction, necrotic focal lesions in organs); 2) delayed type reaction (arthritis, glomerulonephritis, hepatitis, myocarditis, vasculitis, lymphadenopathy). Such complications can be caused by antibiotics, sulfonamides, non-narcotic analgesics, vitamins, aminazine, local anesthetics, sulfonamides, antiepileptic drugs, iodine, mercury, arsenic, etc.

To prevent allergic complications, it is necessary to carefully collect anamnesis. If there is a history of predisposition to allergic diseases, extended-release medications should not be prescribed. A thorough collection of family history will help to identify the presence of idiosyncrasy in the patient - primary intolerance to drugs that is inherited. Idiosyncrasy occurs with drugs such as iodine, quinine, sulfonamides, etc.

Drug therapy withdrawal syndrome is manifested by a sharp exacerbation of the underlying disease. Thus, stopping the use of clonidine for hypertension can provoke the occurrence of a hypertensive crisis with corresponding symptoms.

A side effect can be primary, i.e. associated with a direct effect on certain organs and tissues, or secondary (indirect), not due to the direct effect of the drug on these organs and tissues. For example, non-narcotic analgesics have a direct irritant effect on the mucous membrane of the gastrointestinal tract and cause nausea, vomiting, and the formation of erosions on the gastric mucosa. Therefore, they should be used after meals. This is the primary side effect of non-narcotic analgesics. By affecting kidney enzymes, these drugs retain sodium and water in the body. The appearance of edema is a secondary or indirect effect of non-narcotic analgesics.

Side effects of drugs can manifest as general dysfunctions of the nervous system, gastrointestinal tract, liver, kidneys, cardiovascular system, hematopoietic organs, etc. Some groups of drugs give more specific complications.

Damage to the cardiovascular system is associated with the direct effect of drugs on the heart muscle, causing rhythm and conduction disturbances, a decrease or increase in blood pressure, and impaired myocardial contractility. Hypersensitivity reactions to drugs can cause the development of allergic myocarditis.

Possible disorders of the nervous system (depression, seizures, extrapyramidal disorders, decreased hearing and vision, polyneuropathy, etc.). Nerve cells are highly sensitive to chemicals, so drugs that penetrate the blood-brain barrier can impair performance, cause headaches, dizziness, lethargy, etc. Thus, with prolonged use of antipsychotics, parkinsonism develops, tranquilizers - gait disturbance (ataxia) and depression, stimulating - insomnia, etc. Exposure to drugs sometimes leads to dystrophic changes and even death of nerve fibers and cells. Thus, antibiotics of the aminoglycoside group (streptomycin, gentamicin, neomycin, etc.) can cause damage to the auditory nerve and vestibular apparatus, 8-hydroxyquinoline derivatives (enteroseptol, mexaform, etc.) - optic neuritis, etc. Some drugs also affect on the organ of vision, causing damage to the optic nerve, cataracts, increased intraocular pressure, retinopathy and conjunctivitis.

The liver is a barrier between the intestinal vessels and the general circulatory system. During enteral administration (especially) and during any other administration, it is here that most medicinal substances accumulate and undergo biotransformation. In this case, the liver may be damaged, especially if the drug is concentrated in hepatocytes and retained for a long time - the basis for the manifestation of hepatotoxicity. Cytostatics, some antibiotics, and a number of anti-inflammatory and analgesic drugs have a toxic effect on the liver, causing fatty degeneration, cholestasis, and necrosis of hepatocytes. Some drugs can cause the development of active hepatitis (methyldopa, sulfonamides, anti-tuberculosis drugs, paracetamol). Ethyl alcohol, halogen-containing drugs (fluorothane, aminazine, chloral hydrate, etc.), arsenic and mercury drugs, some antibiotics (tetracycline, streptomycin) and others are highly hepatotoxic. The liver, rich in glycogen and vitamins, is more resistant to the action of chemical agents.

The kidneys, as an excretory organ, concentrate drugs - the basis for the manifestation of nephrotoxicity. Damage to renal tissue is possible during treatment with sulfonamides, antibiotics (streptomycin, gentamicin, cephalosporins, rifampicin), non-steroidal anti-inflammatory drugs (brufen, butadione), thiazide diuretics, etc. Nephrotic syndrome occurs during treatment with D-penicillamine, gold and lithium preparations, tolbutamide, etc. Antibiotics of the aminoglycoside group (streptomycin, gentamicin, neomycin), butadione, sulfonamide drugs, vasoconstrictors, etc. have a nephrotoxic effect. Currently, it is believed that a significant part of nephrological disorders is associated with the occurrence of an allergic process. Calcium preparations, sulfonamides, etc. can cause the formation of stones in the urinary tract with long-term use.

Most drugs used orally affect the mucous membrane of the oral cavity and gastrointestinal tract. Thus, methotrexate leads to serious damage to the mucous membrane of the small intestine. Many anti-inflammatory drugs can cause gastritis, ulceration of the mucous membrane of the stomach and intestines, gastrointestinal bleeding, and exacerbation of pancreatitis. All this is the basis for the ulcerogenic effect (formation of ulcerations on the mucous membranes). Glucocorticoids, non-narcotic analgesics, reserpine, tetracycline, caffeine, etc. are ulcerogenic.

Many medications cause changes in the blood. One of the most dangerous complications of drug therapy is inhibition of hematopoiesis - hematotoxicity. Thus, when using antiepileptic drugs, anemia may occur; chloramphenicol, butadione, amidopyrine, sulfonamide drugs and others - leukopenia up to agranulocytosis, which is often manifested primarily by ulcerative-necrotic lesions of the oral mucosa. Agranulocytosis often develops when non-steroidal anti-inflammatory drugs are prescribed (amidopyrine, indomethacin, butadione), as well as when treated with captopril, chloramphenicol, ceporin, furosemide, etc. Hemolytic anemia occurs when using penicillin, cephalosporins, insulin, chlorpropamide and other drugs. Aplastic anemia is caused by butadiene and other non-steroidal anti-inflammatory drugs, as well as cytostatics, heavy metals, oral hypoglycemic drugs (chlorpropamide, tolbutamide), etc. Thrombocytopenia occurs during therapy with cytostatics, a number of antibiotics, and anti-inflammatory drugs. Vascular thrombosis develops as a result of taking contraceptives containing estrogens and gestogens.

Pharmacotherapy should be carried out with great caution in pregnant women, since many drugs easily penetrate the placental barrier (the porosity of which is especially high in the first 8 weeks of pregnancy) and have a toxic effect on the fetus. A teratogenic effect (teras, teratos - Greek, deformity), that is, causing developmental abnormalities, may have drugs that affect protein synthesis, the exchange of neurotransmitters, blood clotting, etc. Teratogenic effects have been found in glucocorticoids, salicylates, tetracyclines, synthetic antidiabetic drugs, anticonvulsants. Currently, all drugs are necessarily tested for teratogenic effects before being introduced into clinical practice.

Much attention is paid to studying the carcinogenic effects of drugs. Derivatives of benzene, phenol, tar ointments, and cauterizing agents have this activity. Sex hormones and other stimulators of protein synthesis can promote the growth and metastasis of tumors.

With the advent of chemotherapeutic agents, another group of complications associated with the antimicrobial activity of drugs has emerged. The use of antibiotics (penicillin, chloramphenicol) can cause the death and decay of a large number of pathogens and the entry of endotoxin into the blood. This leads to an exacerbation reaction or bacteriolysis. All symptoms of the disease sharply worsen, which requires the use of antitoxic therapy, antihistamines and glucocorticoids.

Broad-spectrum antibacterial drugs, especially antibiotics, suppress microflora that are sensitive to them, promote the proliferation of resistant microorganisms, and dysbacteriosis and superinfection occur. The Candida fungus begins to multiply most often. Candidiasis usually affects the oral mucosa. To prevent this complication, broad-spectrum antibiotics are combined with antifungal agents (nystatin, levorin, decamine).

The use of chemotherapy drugs changes the usual forms of the disease, suppresses the immunological reactivity of the body, changes the antigenic properties of the microorganism, reduces the amount of antigen, and erased forms of infectious diseases arise that do not leave lifelong immunity.

The problem of drug dependence or drug addiction. It was caused by the widespread use of psychotropic drugs. Drug dependence develops to narcotic analgesics, cocaine, sleeping pills, ethyl alcohol, tranquilizers, some stimulants, herbal drugs - hashish, marijuana, opium, etc.

Phenomena of cumulation, addiction and addiction to drugs. Various phenomena may be associated with the use of medications. Thus, with repeated or long-term use of the drug, the phenomenon of cumulation occurs, i.e., an increase in its effect. Cumulation can be the result of the accumulation of a substance (material, chemical cumulation) or the accumulation of dysfunctions (physiological, functional cumulation).

With prolonged and frequent use of the drug, addiction may occur - a decrease in the body's response to repeated use of the drug in the same doses. Addiction manifests itself in the fact that the required therapeutic effect is not achieved when administering the same dose of the drug; in this case, the dose of the drug should be increased or replaced with another drug of similar effect.

The use of drugs that act on the central nervous system (psychotropic drugs) is associated with the phenomenon of addiction, which is a drug dependence on a particular drug caused by its systematic use. Addiction is accompanied by a desire to increase the dose of the drug when taking it again. This is due to the fact that when such drugs are administered, a state of euphoria may occur, characterized by a decrease in unpleasant sensations and leading to a temporary improvement in mood. Addiction to such substances is otherwise called drug addiction.

Drug addiction can be caused by sleeping pills, narcotics, stimulants and painkillers. Accordingly, based on the name of the drug to which the addiction appeared, drug addictions are called alcoholism, etheromania, morphinism, cocaineism, etc. Drug addicts are seriously ill people who need qualified treatment from a medical specialist.

Combining medications (co-administration) can lead to a mutual enhancement of the effect (synergism) or a mutual weakening of it (antagonism). In cases of drug poisoning, it is necessary to use the principles of antagonism.

There are several types of antagonism:

Physico-chemical, based on the absorption of poisons

on the surface of an adsorbent substance (for example, the use of activated carbon for poisoning);

Chemical, based on the interaction of substances,

introduced into the body, as a result of which drugs lose their effect (for example, neutralization of acids with alkalis);

Physiological, based on the administration of drugs,

exerting the opposite effect on a given organ or tissue

action (for example, the introduction of stimulants in case of poisoning with depressants).

A medicinal substance is a chemical compound of natural or synthetic origin, which is the main active principle that determines medicinal properties. Included in the composition of the drug.

Medicinal raw materials are the source of the drug substance. The most common and long-known medicinal raw materials include many plants, both wild and cultivated by specialized farms. The second source of medicinal raw materials is the organs and tissues of various animals, waste products of fungi and bacteria, from which hormones, enzymes, antibiotics and other biologically active substances are obtained. Genetic engineering plays an important role in this, making it possible to obtain previously unknown substances. The third source is some natural and synthetic derivatives. After appropriate processing of medicinal raw materials, an active medicinal substance is obtained.

Depending on the method of processing medicinal raw materials, galenic and new galenic preparations are obtained.

Galenic preparations are preparations of complex chemical composition obtained from parts of plants or animal tissues. They contain active compounds in combination with ballast substances. Herbal preparations include infusions, decoctions, tinctures, extracts, syrups, etc.

New galenic preparations are aqueous-alcoholic extracts from plant medicinal raw materials, highly purified with the removal of all ballast substances. Thanks to this purification, drugs can be administered parenterally.

A drug (medicine) is “any substance or product used or intended to be used to modify or investigate physiological systems or pathological conditions for the benefit of the recipient” (WHO scientific group definition), may contain other substances that provide its stable form. The terms "drug" and "drug" are used interchangeably. The medicine can have a single-component or complex composition that has preventive and therapeutic effectiveness. In the Russian Federation, medicinal products are those that are approved for use by the Ministry of Health in accordance with the established procedure.

A medicinal product is a medicinal product in a form ready for use. This is a dosage medicinal product in a dosage form adequate for individual use and in optimal design with an annotation about its properties and use.

Dosage form - the physical state of the drug, convenient for use (see below).

For all of the above provisions, standards are developed that are approved by government agencies (Pharmacological Committee, Pharmacopoeial Committee).

All drugs are divided into three groups, taking into account their possible toxic effects on the human body if used incorrectly. Lists of these drugs are presented in the State Pharmacopoeia. List A (Venena - poisons) includes medicines, the prescription, use, dosage and storage of which, due to their high toxicity, must be carried out with extreme caution. This list also includes drugs that cause addiction. List B (heroica - potent) includes medicines, the prescription, use, dosage and storage of which must be carried out with caution due to possible complications when used without medical supervision. The third group is drugs dispensed from pharmacies without prescriptions.

A prescription is a written instruction from a doctor to a pharmacist about dispensing or preparing medicines for a patient with instructions for their use. A prescription is a legal document that can only be written by a doctor. A prescription is a doctor’s request to a pharmacist to dispense medication to a patient, indicating the dosage form, dose and method of administration. A prescription is a medical, legal and monetary document in the case of free or discounted medications. The writing of prescriptions and the dispensing of drugs according to them are carried out in accordance with the “Rules for writing prescriptions”, “Rules for storing records and dispensing toxic and potent substances” and other official documents, which are determined by orders of the Ministry of Health of the Russian Federation. Medicines prepared in a pharmacy or at pharmaceutical factories according to the prescription available in the Pharmacopoeia are called official, and those prepared according to doctor’s prescriptions are called manestral.

Drugs from the list of narcotic substances (that can cause drug dependence - drug addiction) are prescribed on special forms. Narcotic analgesics, psychostimulants (amphetamine, dexamphetamine and similar compounds). Narcotic antitussives (codeine, codeine phosphate, ethylmorphine hydrochloride). Sleeping pills (noxiron, etaminal sodium, etc.) Anorexigenic drugs (fepranon, desopimon, etc.) Cocaine hydrochloride, sombrevin.

A prescription for a narcotic drug must be written in the hand of the doctor who signed it and certified with a personal seal and signature. In addition, the prescription is signed by the chief physician of the medical institution or his deputy and certified with a round seal. This order of prescription is determined for drugs with anabolic activity (anabolic steroids) and intoxicating effects - phenobarbital, cyclodol, ephedrine hydrochloride, clonidine (eye drops, ampoules).

On other forms of prescription forms, antipsychotics, tranquilizers, antidepressants, drugs containing ethyl alcohol, etc. are prescribed.

The following medications are dispensed without a prescription, by manual sale: analgin with amidopyrine 0.25 (tab.), Avisan, dekamevit, validol, valerian preparations, Zelenin drops, Vishnevsky ointment, nitroglycerin, etc. It is prohibited to prescribe ether for anesthesia to outpatients , chloroethyl, fentanyl, etc.

Recipes consisting of one medicinal substance are called simple, those containing two or more substances are called complex. In complex prescriptions, the following order of recording medications is used: 1) main medicine; 2) auxiliary agents (strengthening or weakening the effect of the main drug), substances that improve the taste or smell of the drug or reduce its irritating properties (corrective); 3) formative substances (drugs that give the medicine a certain consistency).

Doses of medications. For medications to work properly, they must be used in an adequate dose. A dose is the amount of medicine that is introduced into the body and has a specific effect on it. The strength of the drug is determined by the dose and the order in which it is taken.

Dose is the amount of a medicinal substance introduced into the body, and is expressed in mass or volume units of the decimal system and denoted in Arabic numerals. The number of whole grams is separated by a comma. The unit of weight in the recipe is 1 g - 1.0; per unit volume - 1 ml. When taking medications, it is important to consider that in 1 tbsp. l. contains 15 g of water in 1 tsp. - 5 g; in 1 g of water - 20 drops; in 1 g of alcohol - 47-65 drops.

Depending on the mode of action, the dose can be minimal, therapeutic, toxic or lethal.

Minimum effective (threshold) dose - this is the minimum possible amount of medicine that can have a therapeutic effect.

Therapeutic dose - this is an amount of medicine that exceeds the minimum effective dose, which gives an optimal therapeutic effect and does not have a negative effect on the human body. Most often in medical practice, an average therapeutic dose is used, which in most cases gives an optimal therapeutic effect without pathological effects.

Toxic dose - this is the smallest amount of medicine that can cause a toxic effect on the body. For toxic and potent substances, the maximum single and daily doses for adults and children are indicated in accordance with the age of the patient. In case of an overdose of substances or when replacing one drug with another, poisoning may occur.

Minimum lethal dose is the amount of a drug that can cause death.

Depending on the amount of use per day, the dose can be single (one-time) or daily.

There are also:

Fixed doses. Many drugs have the desired clinical effect in doses below toxic ones (diuretics, analgesics, oral contraceptives, antibacterial agents, etc.), and individual variability is not significant.

Varying doses, difficult to adjust. Adequate dose selection is difficult because the final therapeutic outcome is difficult to quantify, such as depression or anxiety, or the effect develops slowly, such as in thyrotoxicosis or epilepsy, or varies depending on the pathological process (when treated with corticosteroids).

Variable doses, easily adjusted. Vital functions can change significantly and quickly under the influence of drugs, such as blood pressure and blood sugar levels. Dose adjustments can be made quite accurately, since the effect of the drug can be quantified. During corticosteroid replacement therapy, individual doses are also selected.

Maximum tolerated dose. Medicines that do not allow obtaining an ideal therapeutic effect due to undesirable reactions (anticancer, antibacterial) are used in maximum tolerated doses, i.e. they are increased until adverse reactions appear, and then slightly reduced.

Minimum tolerated dose. This dosing principle is used less frequently, usually with long-term administration of corticosteroids for inflammatory and immunological diseases, for example, bronchial asthma, rheumatoid arthritis. The dose to produce symptomatic improvement may be so high that severe adverse reactions are inevitable. The patient receives a dose that alleviates his condition and is safe. This is a difficult task.

The initial dose provides the desired effect and does not cause toxic reactions. Often the same as the maintenance dose, ensuring the stability of the therapeutic effect.

Vitamins are organic substances that are not synthesized in the body or synthesized in insufficient quantities, supplied with food and combined into a single group based on their absolute necessity for the body.

Vitamins play a primary role in metabolism, regulation of the processes of absorption and use of basic nutrients - proteins, fats (lipids) and carbohydrates, as well as in maintaining the normal physiological state of the nervous, cardiovascular, digestive, genitourinary, endocrine and hematopoietic systems. Consuming sufficient amounts of vitamins helps strengthen the body, increase its performance and resistance to harmful environmental influences.

Lack or absence of vitamins leads to weakening of the body and the development of characteristic diseases - hypo- and avitaminosis, in which metabolism and most body functions are disrupted. Hypervitaminosis is an excessive intake of vitamins into the body. The lack of vitamins is felt especially in the spring, when the consumption of vegetables, fruits and berries is reduced, and when the content of vitamins in them, especially C and P, drops. At the same time, people experience weakness, increased fatigue, decreased performance and a decrease in the body's resistance to infections.

Exhibiting high biological activity in very small doses, vitamins are necessary:

For normal cellular metabolism and tissue trophism

For energy transformation

For plastic exchange

To maintain vital functions such as reproduction, growth and tissue regeneration

To ensure the body's immunological reactivity

For the normal functioning of all organs and tissues.

Pharmacotherapy is inextricably linked with toxicology.

WAYS OF ADMINISTRATION OF MEDICINES INTO THE BODY

There are enteral routes of administration through the digestive tract and parenteral routes, bypassing the digestive tract.

Enteral routes of administration

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1. The number of drugs used should be limited to the minimum necessary; simultaneous administration of more than three drugs on an outpatient basis is undesirable.
2. When combining synergistic drugs, the dose of each of them is reduced by 1.5-2 times.
3. It is advisable to simplify the medication regimen as much as possible, giving preference to long-acting drugs.
4. If long-term therapy is necessary, the cost-effectiveness ratio of the drugs and the financial capabilities of the patient should be taken into account.
5. It is necessary to inform the patient about the goals and duration of treatment, expected results, the principle of action of the prescribed medications, warn about possible side effects and their recognition. interaction of drugs with alcohol, effect on driving, etc. The regimen for taking medications should be discussed (and written down!) in detail, indicate the time and method of taking the medication, and the patient’s actions in case of forced or accidental skipping of a dose.
6. You should strive to ensure that the desired therapeutic effect is provided by the smallest effective dose of the drug.
7. Dosing tactics (gradual increase in dose, impact dose with transition to maintenance doses, stable maintenance dose, gradual dose reduction, etc.) depend on the specifics of the drug used and the clinical situation.
8. When adjusting the dose, it is not recommended to increase it by more than 50% of the original.
9. An adequate assessment of the results of dose adjustment is possible no earlier than after 4 half-lives of the drug, provided that it is taken regularly (it is also necessary to make an adjustment for the timing of the development of the pharmacological effect).
10. The withdrawal of some medications should be done gradually (corticosteroids, beta-blockers, clofellip, H 2 blockers). It is necessary to warn the patient about this.
11. It is necessary to develop a high level of adherence to the prescribed treatment in the patient.
12. If there is no expected effect, possible reasons should be analyzed.

Reasons for the failure of drug therapy

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1. Incorrect diagnosis.
2. Inadequate choice of drug(s).
3. Irrational or difficult to implement medication regimen (too frequent use, large number of medications, inconvenient dosage forms, high cost of treatment, etc.).
4. Adverse drug interactions; inappropriate combination or antagonism with other drugs used simultaneously for other purposes.
5. Insufficient doses of medications.
6. Negative impact of concomitant pathology.
7. Phenomena that develop with long-term drug use: the development of tolerance (the “escape” effect), a pronounced “after-effect” phenomenon, “withdrawal” syndrome, etc.
8. Low patient adherence to treatment (irregular medication intake, premature cessation of treatment, refusal of treatment, dementia and mental disorders, aggravation to malingering).

Ways to increase patient adherence to prescribed treatment

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Low patient adherence to treatment is one of the most important reasons for the ineffectiveness or lack of effectiveness of drug therapy for various chronic diseases.

Ways to improve the situation.

• Find out the patient's attitude towards the treatment being carried out.
• Set a clear goal and perspective for treatment.
• If long-term or lifelong treatment is necessary, educate the patient about the importance of long-term therapy, its safety, and its benefits.
• Explain in detail to the patient (or relatives) the medication regimen and write it down on paper.
• Inform the patient about his disease, involve the patient and his relatives in the treatment process.
• Accustom the patient to daily analysis of his condition, measuring blood pressure, peak flowmetry, monitoring blood sugar and urine, etc.
• Introduce taking medications into your daily routine (time it in conjunction with hygiene procedures, eating food, etc.).
• Encourage lifestyle changes necessary for successful treatment (cessation of smoking, alcohol, weight loss, etc.).
• Maintain contact with patients, plan a clear schedule for regular visits.
• Make treatment as simple and inexpensive as possible.
• Be aware of the possible side effects of treatment, try to prevent, reduce or alleviate them.
• Support the patient's desire to achieve the treatment goal. Find the strength to stop unsuccessful treatment and find the right approach.

For quotation: Nasonov E.L. Pharmacotherapy of rheumatoid arthritis from the perspective of evidence-based medicine: new recommendations // RMJ. 2002. No. 6. P. 294

Institute of Rheumatology RAMS, Moscow

R Eumatoid arthritis (RA) is an autoimmune disease of unknown etiology, characterized by symmetrical erosive arthritis (synovitis) and a wide range of extra-articular (systemic) manifestations. RA is an extremely common disease, affecting approximately 1% of the world's population. The cardinal signs of RA include steadily progressive joint damage (chronic pain, deformation, dysfunction), leading to disability and even a decrease in the life expectancy of patients (Fig. 1).

Rice. 1. Rheumatoid arthritis: variants of the course

The development and progression of RA is determined by a complex combination of genetically determined and acquired defects (“imbalance”) of normal (immuno) regulatory mechanisms that limit the pathological activation of the immune system in response to potentially pathogenic and often physiological stimuli. This leads to a rapid transformation of the physiological (protective) acute inflammatory response into chronic progressive inflammation, which is an integral feature of RA. In RA, the Th1 type of immune response predominates, characterized by hyperproduction of “pro-inflammatory” cytokines, such as interleukin (IL)-1, tumor necrosis factor (TNF)-a (Fig. 2). It should be especially emphasized that the progression of RA is a dynamically developing process, which (both from the point of view of pathogenetic mechanisms and clinical, instrumental and laboratory manifestations) is conventionally divided into several stages:

Rice. 2. The role of cytokines in the development of rheumatoid arthritis

• early (asymptomatic) stage, characterized by vascular and cellular activation;
• advanced (rapid chronicization of inflammation) stage, manifested by impaired angiogenesis, endothelial activation, cell migration, infiltration of synovial tissue by activated CD4+ T lymphocytes, formation of rheumatoid factors and immune complexes, synthesis of “pro-inflammatory” cytokines, prostaglandins, collagenase, metalloproteinases;
• late stage, characterized by somatic mutation and defects in apoptosis of synovial cells.

The etiology of RA is unknown , which makes it impossible to carry out effective etiotropic therapy. Therefore, treatment of RA remains one of the most difficult problems of modern clinical medicine and pharmacology. However, deciphering the pathogenetic mechanisms underlying rheumatoid inflammation served as the basis for developing the concept “pathogenetic (basic) therapy” , which was formed more than 10 years ago. The “basic” drugs include a large number of drugs that differ in chemical structure and pharmacological properties. They are united by the ability, to a greater or lesser extent and through various mechanisms, to suppress inflammation and/or pathological activation of the immune system. The progress made in the treatment of RA in recent years is very clearly visible when comparing the International Guidelines (American College of Rheumatology) for the pharmacotherapy of RA, published in 1996 and 2002. During this time, new “symptomatic” (COX-2 inhibitors) and basic (leflunomide, “anti-cytokines”) drugs have been developed (Fig. 3), most importantly, the concept of “early” aggressive therapy for RA has been more clearly formulated.

Rice. 3. Modern pharmacotherapy of rheumatoid arthritis

Treatment of rheumatoid arthritis

The main objectives of pharmacotherapy for RA are presented in Figure 4. In recent years, it has become especially obvious that the highest rate of increase in radiological changes in joints is observed precisely in the early stages of RA , which correlates with a poor prognosis. Since the use of “basic” drugs for “early” RA makes it possible to modify the course of the disease, treatment of RA (as well as many other chronic human diseases, such as diabetes mellitus, arterial hypertension, coronary artery disease, etc.) should begin as early as possible, preferably during the first 3 months after making a definite diagnosis of RA (Fig. 5). This is especially important in patients with risk factors for poor prognosis, which include high titers of rheumatoid factor, a marked increase in ESR, damage to more than 20 joints, the presence of extra-articular manifestations (rheumatoid nodules, Sjogren's syndrome, episcleritis and scleritis, interstitial lung disease, pericarditis, systemic vasculitis, Felty's syndrome). For example, in seropositive patients with polyarthritis at the onset of the disease, the likelihood of severe erosive joint damage during the first two years of the disease is extremely high (70%).

Rice. 4. Objectives of therapy for rheumatoid arthritis

Rice. 5. The importance of early aggressive treatment for rheumatoid arthritis

At the same time, attention should be paid to the difficulties of differential diagnosis of “early” RA (< 6-12 мес от начала симптомов) от ряда других ревматических и неревматических заболеваний (грипп, краснуха, парвовирус В19, корь, гепатит, лайм-боррелиоз, серонегативные спондилоартропатии, микрокристаллические артриты, ревматическая лихорадка, СЗСТ, остеоартроз, ревматическая полимиалгия, системные васкулиты, опухолевый артрит и др.), которые могут начинаться с «ревматоидоподобного» поражения суставов. Ниже суммированы клинические и лабораторные признаки, позволяющие заподозрить дебют РА, при наличии которых пациент должен быть незамедлительно направлен на консультацию к врачу-ревматологу (рис. 6). После постановки достоверного диагноза РА (рис. 7) всем больным необходимо провести базовое клиническое (рис. 8), лабораторное и инструментальное (рис. 9) обследование.

Rice. 6. Clinical signs to suspect rheumatoid arthritis

Rice. 7. Criteria for the diagnosis of rheumatoid arthritis

Rice. 8. Clinical examination of patients with rheumatoid arthritis

Rice. 9. Laboratory and instrumental examination of patients with rheumatoid arthritis

At each patient visit, the rheumatologist should assess disease activity (Fig. 10). International criteria for the effectiveness of therapy and clinical remission have been developed. According to the criteria of the American College of Rheumatology (ACR), evidence of therapy effectiveness may include a 20% improvement (ACR20) in swollen and painful joint scores , along with a 20% improvement in 3 out of 5 of the following parameters: overall assessment of the effectiveness of treatment in the opinion of the doctor and the patient, assessment of the intensity of pain in the opinion of the patient, assessment of the degree of disability and “acute-phase” indicators (Fig. 11). Assessment of radiographic progression using the Sharp method allows one to evaluate the effect of therapy on the outcome of the disease (Fig. 12).

Rice. 10. Assessment of the activity of rheumatoid arthritis

Rice. 11. Criteria for treatment effectiveness (ACR20 / ACR50 / ACR70)

Rice. 12. Modified Sharp method

Nonsteroidal anti-inflammatory drugs

A general plan for the management of RA patients is presented in Figure 13. The main method of symptomatic treatment of RA is the prescription of non-steroidal anti-inflammatory drugs (NSAID) to reduce pain and inflammation in joints . Conventionally, NSAIDs are divided into short-lived ones (diclofenac, ketoprofen, lornoxicam (Xefocam) etc.) (< 6 часов) и длительно-живущие (пироксикам, напроксен и др.) (> 6 hours). However, there is no clear relationship between the plasma half-life of NSAIDs and its clinical efficacy. “Short-lived” drugs can accumulate for a long time and in high concentrations in the area of ​​inflammation, for example, in the joint cavity. Therefore, one or two doses of “short-living” drugs are often as effective as multiple doses. When choosing an NSAID, a number of factors must be taken into account: effectiveness, tolerability, safety and cost of the drugs. In patients with risk factors for gastrointestinal complications, the drugs of choice are so-called selective cyclooxygenase (COX)-2 inhibitors. A limitation of NSAID monotherapy is that these drugs rarely completely suppress the clinical manifestations of arthritis, do not affect the progression of joint damage, and cause side effects, especially in the elderly. Risk factors for gastrointestinal side effects include older age (over 75 years), a history of peptic ulcers, concomitant use of glucocorticosteroids, severe concomitant diseases, taking high doses of NSAIDs or simultaneous use of several drugs. For the prevention and treatment of NSAID-induced gastrointestinal lesions, H2-histamine receptor blockers (high doses only), proton pump inhibitors and misoprostol can be used. It should be emphasized: although the symptoms of dyspepsia, which very often occur while taking NSAIDs, are often relieved by low doses of H2-histamine receptor blockers, their use not only does not reduce, but may even increase the risk of severe complications from the gastrointestinal tract (perforations, perforated ulcers and gastric bleeding). Although selective COX-2 inhibitors are significantly less likely to cause gastrointestinal damage than “standard” NSAIDs, their use may also cause undesirable effects, including symptoms of dyspepsia, delayed healing of gastric and duodenal ulcers, fluid retention, and increased blood pressure. In addition, one study showed that RA patients taking a selective COX-2 inhibitor (rofecoxib) had a higher incidence of thrombotic complications (myocardial infarction) than patients taking naproxen. However, data from other studies indicate that the use of other selective COX-2 inhibitors, meloxicam and celecoxib, does not lead to an increase in the incidence of cardiovascular thrombosis compared with patients taking “standard” NSAIDs. The use of both “standard” NSAIDs and selective COX-2 inhibitors should be carried out with extreme caution in patients with reduced intravascular volume or edema associated with congestive heart failure, nephrotic syndrome, cirrhosis and with an increase in creatinine of more than 2.5 mg%.

Rice. 13. Management of patients with rheumatoid arthritis

Glucocorticoids

Treatment with low (< 10 мг/сут) дозами глюкокортикоидов (ГКС) нередко allows adequate control of rheumatoid inflammation , not inferior in this regard to “basic” antirheumatic drugs with an acceptable toxicity profile, a decrease in the rate of radiological progression in patients with “early” active RA (especially when combined with methotrexate). The administration of GCS is especially indicated in patients who do not respond to NSAIDs or have contraindications for their administration in an adequate dose. Unfortunately, in many patients, an attempt to discontinue GCS leads to an exacerbation of synovitis, even despite the use of “basic” drugs, that is, a functional glucocorticoid dependence develops.

Treatment with low (< 10 мг/сут) дозами глюкокортикоидов (ГКС) нередко, не уступая в этом отношении «базисным» противоревматическим препаратам приемлемым профилем токсичности, снижением скорости рентгенологического прогрессирования у больных с «ранним» активным РА (особенно при сочетанном применении с метотрексатом). Особенно показано назначение ГКС у пациентов, не отвечающих на НПВП или имеющих противопоказания для их назначения в адекватной дозе. К сожалению, у многих пациентов попытка отмены ГКС приводит к обострению синовита, даже несмотря на использование «базисных» препаратов, то есть развивается функциональная глюкокортикоидная зависимость.

Pulse therapy GCS (methylprednisolone, dexamethasone) allows you to achieve rapid (within 24 hours), but short-term (3-12 weeks) suppression of the activity of the inflammatory process, even in patients resistant to previous therapy. However, the effect of pulse therapy on the radiographic progression of joint damage has not been proven.

Local GCS therapy has an auxiliary value. Its goal is to suppress active synovitis at the onset of the disease and its exacerbations in 1 or more joints, and improve joint function. However, glucocorticoids affect only the local process (and RA is a systemic disease) and cause only temporary improvement. The most effective are long-acting glucocorticoids (triamcinolone, methylprednisolone) and especially betamethasone. It should be borne in mind that not every exacerbation of monoarthritis in RA is associated with the activity of the disease itself; it may be a manifestation of infectious or microcrystalline arthritis. It is not recommended to perform repeated injections of GCS into the same joint more often than once every three months. The need for more frequent injections may reflect the inadequacy of “background” therapy.

Although RA patients tend to develop osteoporosis regardless of glucocorticoid therapy, patients receiving even low doses of oral corticosteroids have an increased risk of osteoporotic fractures. This dictates the need for periodic determination of bone mineral density (BMD) using bone densitometry methods (approximately once every 12 months) and mandatory administration of calcium supplements (1500 mg) and colecalciferol (400-800 IU per day) from the moment of GCS administration. If effectiveness is insufficient, it is advisable to use other antiosteoporetic drugs, such as bisphosphonates and calcitonin.

Basic therapy

The effectiveness of “basic” drugs in the form of mono- (Table 1) or combination (Table 2) therapy in controlling the symptoms of joint damage, a positive effect on radiological progression, functional status and quality of life, has been strictly proven in placebo-controlled studies. It is believed that their use can reduce the overall cost of medical care for patients, and early initiation of adequate “basic” therapy can help increase the life expectancy of RA patients. Indications for immediate (within 3 months) prescription of “basic” drugs is definite RA, in which, despite the use of NSAIDs in adequate doses, joint pain, morning stiffness (or general malaise), active synovitis, persistent increase in ESR or CRP, and/or signs of erosive joint damage persist.

Characteristics of the “basic” drugs used to treat RA are presented in Tables 3 and 4. “Basic” therapy reduces the need for NSAIDs and glucocorticoids (and therefore the likelihood of developing side effects that occur during treatment with these drugs), improves the quality of life and long-term prognosis. The “disadvantages” of basic therapy include the need for careful monitoring of the development of side effects (Table 5-7).

The choice of one or another “basic” drug depends on a number of subjective and objective factors and should be individualized whenever possible. Unfortunately, relatively few studies have been devoted to comparing the effectiveness and safety of various disease-modifying drugs and combination therapy with several disease-modifying drugs. In women of childbearing age, while taking most of the “basic” drugs, effective contraception is necessary, and in the event of pregnancy or breastfeeding, the regimen for taking the “basic” drugs must be modified.

Given the high safety, many rheumatologists prefer to start “basic” therapy with a prescription hydroxychloroquine or sulfasalazine , the effectiveness of which (especially in patients with “early” RA) with moderate activity has been proven in many studies. Although hydroxychloroquine monotherapy does not slow the radiographic progression of joint damage, it is generally quite effective in improving the long-term prognosis of the disease. Sulfasalazine suppresses inflammation more quickly than hydroxychloroquine within the first month of starting therapy. In addition, during treatment there is a slowdown in the radiological progression of the disease. Side effects such as nausea and abdominal pain are moderate and usually develop during the first few months of therapy. The incidence of side effects decreases with slowly increasing the dose of the drug. However, leukopenia and other more severe side effects can develop during any period of treatment, which dictates the need for periodic laboratory examination. If there is no clinical effect within 4 months, it is necessary to prescribe another “basic” drug.

In patients with “active” RA or those with risk factors for poor prognosis, the drug of choice is methotrexate , which has the most favorable efficacy/toxicity ratio. This allows us to consider it as “gold standard” of pharmacotherapy for RA when testing the effectiveness and safety of new “background” drugs. There is evidence that more than 50% of RA patients can take methotrexate for more than 3 years, which is significantly longer than other “basic” drugs. In general, discontinuation of methotrexate treatment is more often associated with the development of side effects than with treatment failure. The incidence of many side effects (stomatitis, nausea, diarrhea, alopecia) can be reduced by prescribing folic acid, without loss of effectiveness. Relative contraindications for prescribing methotrexate are liver disease, significant renal impairment, lung disease and alcohol abuse. Although the most common side effect is increased liver enzymes, the risk of severe liver damage is low. Liver biopsy is indicated only in patients with persistent increases in liver enzyme levels after discontinuation of the drug.

Patients who are contraindicated for treatment with methotrexate, who fail to achieve sustained clinical improvement or develop side effects during treatment with methotrexate (up to 25 mg/week), are advised to prescribe a new “basic” drug leflunomide , "biological" agents , or other “basic” drugs in the form of mono- or combination therapy (Fig. 14). A decrease in RA activity and a slowdown in radiological progression during treatment with leflunomide is expressed to the same extent as with methotrexate. In addition, leflunomide can be successfully used in combination with methotrexate in patients in whom methotrexate monotherapy is insufficiently effective. However, in patients receiving combination therapy with methotrexate and leflunomide, an increase in the concentration of liver enzymes is observed significantly more often than during leflunomide monotherapy. It must be borne in mind that since the metabolism of leflunomide depends on the hepatic enteric circulation, this drug has a very long half-life and can remain in the body for more than 2 years. To eliminate it, it is recommended to use cholestyramine. Contraindications for the use of leflunomide are liver disease, immunodeficiency, and the use of rimfapicin, which causes an increase in the concentration of leflunomide.

Rice. 14. Tactics for managing patients with rheumatoid arthritis when methotrexate is ineffective

Effective drugs for the treatment of RA include gold salts. D-penicillamine and cyclosporine A are now used less frequently, primarily due to side effects. For example, against the background of D-penicillamine, the development of autoimmune syndromes (myasthenia gravis, Goodpasture syndrome, polymyositis) has been described. Long-term use of cyclosporine A is limited by the development of arterial hypertension and dose-dependent renal dysfunction, which sometimes persists after discontinuation of the drug. In addition, many drugs can cause an increase in serum levels of cyclosporine A and thus contribute to the nephrotoxicity of the latter. Therefore, cyclosoporin A is recommended to be used primarily in RA patients who are “refractory” to other “basic” drugs.

Anticytokine therapy

One of the most striking achievements in the pharmacotherapy of RA is associated with the development of a fundamentally new group of drugs, which are called “biological” agents, the mechanism of action of which is associated with the suppression of the synthesis of “pro-inflammatory” cytokines - TNF-a and IL-1, playing, as already noted, a fundamental role in the immunopathogenesis of RA. Currently, 3 groups of drugs are used in the treatment of RA, 2 of which are monoclonal antibodies (mAbs) to TNF-a - infliximab (Remicade) and recombinant soluble TNF-a receptor coupled to the Fc fragment of IgG (Etanercept) - inhibit the synthesis and biological effects of TNF-a and recombinant soluble IL-1 antagonist (Anakinra), which suppresses the functional activity of IL-1. Data have been obtained that the use of biological inhibitors of TNF-a and IL-1 can reduce the activity of the immunopathological process and achieve a clinical effect, improve the quality of life and slow down the radiological progression of joint damage, even in patients resistant to previous therapy with standard “basic” drugs. All drugs are effective in combination with methotrexate in patients with active RA who do not respond to methotrexate monotherapy. Infliximab is approved for use in combination with methotrexate, and Etanercept and Anakinra are approved for use as monotherapy or in combination with other “background” drugs, with the exception of “biological” TNF-a inhibitors.

Extracorporeal procedures

In the complex treatment of severe RA, resistant to standard “basic” therapy, it is advisable to prescribe various extracorporeal procedures, including plasmapheresis And immunoadsorption using protein A of staphylococcus .

Combination therapy

Since monotherapy with “basic” drugs in many cases does not control the progression of RA, the possibility of using combination therapy with several “basic” drugs (Table 2). The most well-studied combinations are cyclosporine and methotrexate and “triple” therapy with methotrexate, sulfasalazine and hydroxychlorquine. It should be emphasized, however, that although the combination of cyclosporine and methotrexate is more effective than methotrexate monotherapy, with long-term use in some patients the development of arterial hypertension and an increase in creatinine levels was noted.

A more promising direction for the treatment of RA seems to be combination therapy with “basic” (methotrexate, leflunomide) and “biological” (infliximab, etc.) drugs.

Non-pharmacological treatments

To prevent the progression of joint deformation, the pattern of motor activity should be changed. For example, to prevent the development of ulnar deviation, the hand should perform radial rather than ulnar flexion: open the tap and turn the key in the lock not with the right hand, but with the left hand, etc. An important component of the treatment of RA is physical therapy . For light to moderate activity, different methods are indicated physiotherapy , especially laser irradiation of affected joints. Sanatorium-resort treatment is indicated only for patients with minimal RA activity or in remission. As orthopedic aid orthoses are used - special devices made of thermoplastic, worn while sleeping and holding the joint in the correct position. Prosthetics of hip and knee joints and surgical treatment of deformities of the hands and feet are widely used.

Thus, over the past 5 years, significant progress has been made in the treatment of RA, significantly greater than in all previous years. We hope that the practical use of the presented recommendations, based on international experience in the treatment of RA and “evidence medicine,” will significantly improve the prognosis of this serious disease.

Literature:

1. Nasonov E.L. Anti-inflammatory therapy for rheumatic diseases. Moscow, M-CITY Publishing House, 1996, 345 pp.

2. Nasonov E.L. Non-steroidal anti-inflammatory drugs (Prospects for use in medicine) Moscow, Anko, 2000 Moscow,

3. Nasonov E.L. Nonsteroidal anti-inflammatory drugs for rheumatic diseases: standards for the treatment of breast cancer, 2001; 9, 7-8;265-270.

4. Nasonov E.L. Prospects for pharmacotherapy of inflammatory rheumatic diseases: monoclonal antibodies to tumor necrosis factor. RMJ, 2001, 9, 7-9, 280-284

5. Nasonov E.D., Skripnikova I.A., Nasonova V.A. The problem of osteoporosis in rheumatology. Moscow. "STIN", 1997; 429 pp.

6. Sigidin Ya.A., Lukina G.V. Rheumatoid arthritis. Moscow, ANKO, 2001, 328 pp.

7. Harris E,D. Jr. Rheumatoid Arthritis: pathophysiology and implications for therapy. N.Engl. J Med 1990;322:1277-1289

8. American College of Rheumatology Ad Hoc Commitee on Clinical Guidelines. Guidelines for the management of rheumatoid arthritis. Arthritis Rheum 1996;39:713-722.

9. American College of Rheumatology Ad Hoc Commitee on Clinical Guidelines. Guidelines for monitoring drug therapy in rheumatoid arthritis. Arthritis Rheum 1996;39:723-731.

10. American College of Rheumatology Subcommittee on Rheumatoid Arthritis Guidelines. Guidelines for the Management of Rheumatoid Arthritis. 2002 Update. Arthritis Rheumatism.2002;46:328-346.

Angina pectoris is the most common manifestation of coronary heart disease (CHD) in our country. According to statistics for 2003, angina pectoris was detected in 2,720,000 residents of Ukraine, which is 37% of all cases of diagnosed IHD (7,272,619) and 40% of all cases of newly diagnosed IHD (258,337).

N.N. Bezyuk, Candidate of Medical Sciences, Department of Faculty Therapy No. 1 of the National Medical University named after. A.A. Bogomolets, Kyiv

How important is the problem of angina pectoris?

This corresponds to data obtained in the UK, where an analysis of 295,584 cases of newly diagnosed IHD found that angina pectoris was the most common first manifestation of IHD - 46%, myocardial infarction - 27%, sudden death - 14% and unstable angina - 13% (Sutcliffe S. et al., 2003). Moreover, the average incidence of angina pectoris per year is 213 per 100,000 population over 30 years of age (Elveback L. et al., 1986).

The prevalence of angina in Ukraine compared to 1999 has increased by 64% and is approximately 2 times higher (5.7% of the population) than in the USA (3.8% of the population). At the same time, mortality from IHD in the structure of all causes of death in Ukraine is also 2 times higher than the European average and US statistics (41%, 22% and 20%, respectively; British Heart Foundation. European Cardiovascular Disease Statistics 2000).

Consequences of angina pectoris. The occurrence of angina leads not only to a deterioration in the quality of life (decreased tolerance to physical and psycho-emotional stress), but also increases the risk of unstable angina and the development of MI by 3 times, and therefore leads to an increased risk of death. During the first year after the onset of angina, 10% of patients develop MI or die, and another 20% require revascularization (Gandhi M. et al., 1995). According to various sources, angina pectoris precedes from 20 to 50% of all cases of MI (Rouleau J., 1996; Hurst W., 2002).

Angina pectoris is not only direct costs for outpatient and inpatient examinations and payment for treatment, but also indirect costs associated with temporary and permanent disability of the patient, which are a heavy burden for society, healthcare, patients and their families. For example, in the UK in 2000, for 635,000 patients with angina, there were 2.35 million doctor visits, 16 million prescriptions, 149,000 hospitalizations, 117,000 angiographies, 21,400 CABG and 17,700 PTCA (Stewart S., Eur. Heart J., 2002, 4, 720).

If angina is not diagnosed in a timely manner, this will result in the patient not receiving adequate treatment that could improve the quality and length of his life. The consequence will be progression of symptoms and complications (MI or death) in high-risk individuals. IHD is the cause of death for approximately every second resident of our country.

Problems of pharmacological treatment of angina pectoris. The following traditional and interrelated problems of angina pectoris can be distinguished: poor diagnosis and inadequate treatment. Poor diagnosis can lead to the labeling of “angina pectoris” and, as a result, to the prescription of unnecessary treatment, an increase in the level of neuroticism, unnecessary additional examination and hospitalization, as well as to the lack of effect of treatment.

Specific problems in the pharmacological treatment of angina are as follows.

1. Treatment of atypical pain syndrome as classical angina (diagnosis not verified).
2. Insufficient treatment:
   • low doses of antianginal drugs;
   • lack of heart rate control during treatment with β-blockers.
3. Polypharmacy (many unnecessary drugs).
4. Risk factors are not identified and corrected.

The goal of treatment for stable angina. When starting to treat patients with stable angina, it is necessary to clearly understand that there are only two goals for treating patients with this diagnosis. The first is the prevention of MI and death, which means prolongation of life. The second is a reduction in the symptoms of angina pectoris, which leads to an improvement in the quality of life. Naturally, treatment aimed at prolonging life is a priority. In the event that there are two different methods of treatment (drugs) that are equally effective in eliminating the symptoms of angina pectoris, the type of treatment that prolongs life is preferred.

Improving the quality of life and prognosis of the disease requires, on the one hand, an accurate diagnosis of stable angina, and on the other, determining the degree of risk of complications. The choice of the right treatment depends on this, since it varies depending on the goal.

A necessary condition for effective treatment is also a good knowledge of the patient about the essence of his illness and an understanding of the meaning of treatment. For most patients, the goal of treatment should be complete or almost complete elimination of anginal pain and a return to normal life and functional abilities corresponding to functional class I angina. 82% of patients with stable angina pectoris limit daily activities in order to avoid angina attacks, and strive to increase sleep and rest time. (Chestnut L. G. et al., Measuring Heart Patients’ Willingness to Pay for Changes in Angina Symptoms: Some Methodological Implications // Journal of Medical Decision Making, 1996, Vol. 16. 65-77).

However, for an elderly patient with severe angina and several comorbidities, symptomatic relief may be sufficient to allow only limited exercise.

Sometimes it can be quite difficult to assess such a subjective indicator as quality of life, and often there is a discrepancy between the opinions of the doctor and the patient. The doctor may believe that the prescribed treatment controls angina attacks, while the patient is sure of the opposite. In a UK study of 5,125 patients with angina, half of the patients reported two or more angina attacks per week, but 62% of patients described their health status as “poor” or “poor” (Pepine C.J. et al Characteristics of a Contemporary Population with Angina Pectioris // American Journal of Cardiology, 1994, Vol. 74. 226-231).

What are the current treatment recommendations for stable angina? We should use the European Society of Cardiology (ESC, 1997) guidelines for the treatment of stable angina, the more recent American Heart Association (AHA/AHA, 2002) guidelines, and the most recent American College of Physicians (ACP, 2004) guidelines. In the spring of 2005, the emergence of new recommendations for the treatment of stable angina of the European Society of Cardiology was announced, since it is clear that the current ESC recommendations are already significantly outdated.

Drug treatment of angina aimed at preventing MI and death

Antiplatelet drugs. The growing importance of antithrombotic drugs has led to the publication of separately developed recommendations from the European Society of Cardiology on their use (Patrono C. et al., 2004). Drugs of this class should be prescribed routinely and long-term to all patients diagnosed with coronary artery disease, even in cases where there are no symptoms of angina pectoris. According to these recommendations, the drugs of choice are aspirin at a dose of 75-150 mg per day and clopidogrel 75 mg per day.

The importance of clopidogrel, the only antiplatelet drug proven better than aspirin in the prevention of MI, stroke and vascular death, is growing. The combination of aspirin and clopidogrel leads to an even greater increase in the effectiveness of treatment. This is necessary when the patient has already suffered any complication of atherothrombosis - acute coronary syndrome or stroke, as well as after coronary angioplasty. Dipyridamole should no longer be used for ischemic heart disease, either as monotherapy or in combination, as it can provoke myocardial ischemia (Patrono C. et al., 2004).

β-Blockers. Indicated for long-term use in all patients with coronary artery disease in the absence of contraindications, as it has been proven to improve survival, the incidence of recurrent myocardial infarction and the symptoms of ischemia. Diabetes mellitus is no longer a contraindication to the use of β-blockers - their effectiveness in these patients is even higher. In the recommendations of the European Society of Cardiology, beta-blockers are recommended as initial treatment in the absence of contraindications, especially in patients who have had a myocardial infarction, as they have been proven to reduce mortality (Swedberg K. et al., 2004).

In the presence of bradycardia, sinus node dysfunction, or AV block, β-blockers may result in symptomatic bradycardia or higher degrees of block. In addition, β-blockers are contraindicated in patients with bronchial asthma. In patients with obstructive pulmonary diseases, insulin-dependent diabetes mellitus and severe vascular pathology of the lower extremities, treatment should begin with very small doses.

The higher the patient's resting heart rate, the higher the effectiveness of β-blockers. The decrease in heart rate during treatment can reach 55 per minute, provided that it is well tolerated and there is no symptomatic hypotension. Preference is given to drugs without intrinsic sympathomimetic activity. The basic principle of using β-blockers is to prescribe them in doses that provide a clear effect of blocking β-adrenergic receptors. To do this, it is necessary to achieve a reduction in heart rate at rest to 55-60 per minute, which is not always achieved in real clinical practice and is accompanied by an insufficiently pronounced effect.

Lipid-lowering drugs. Statins should be prescribed to all patients with coronary artery disease. The question remains, what should the target level of LDL reduction be? Until now, this level has been less than 100 mg/dL.

However, in 2004, revolutionary changes occurred in the field of lipid-lowering therapy. Based on the results of the latest HPS and PROVE IT studies, a specially published addition to the generally accepted NCEP ATP III recommendations in the group of high-risk patients (diabetes mellitus, metabolic syndrome, smokers, post-acute coronary syndrome) recommends a new target level for reducing LDL levels - less than 70 mg /dl (Grundy S. et al., 2004).

Currently, all statins available to us have randomized trials with “hard endpoints” and can be used in patients with angina pectoris. The greatest evidence base for the effectiveness and safety of treatment is simvastatin, pravastatin and atorvastatin.

ACE inhibitors. The recently published expert consensus of the European Society of Cardiology on the use of ACE inhibitors in CVD (2004) indicates that the use of this group of drugs is mandatory for left ventricular dysfunction and/or heart failure. In coronary artery disease without heart failure and left ventricular dysfunction, effectiveness in reducing mortality has been proven only for the tissue ACE inhibitors ramipril and perindopril. Only for these drugs the theoretical premises and experimental data were confirmed in the large randomized controlled studies HOPE and EUROPA. The research results are so convincing that they have led to the addition of a new indication for ACE inhibitors - secondary prevention of cardiovascular disease without heart failure or left ventricular dysfunction (ESC, 2004). And in October 2004, the American College of Physicians (ACP), based on these studies, recommended taking ACE inhibitors to all patients with stable angina, asymptomatic suspected or established coronary artery disease.

The degree of reduction in the risk of death in patients with coronary artery disease depends on the number of drug classes used. The risk of death is lowest with the simultaneous use of drugs from all four classes mentioned. With such complex treatment, the greatest currently possible degree of reduction in the risk of complications of coronary artery disease and death is achieved.

Drug treatment of angina pectoris aimed at eliminating symptoms. Three classes of antianginal drugs are used in the treatment of angina: β-blockers, long-acting calcium antagonists and nitrates, long-acting and short-acting (to relieve an attack of angina). Drugs of all these classes have proven effectiveness in reducing the incidence of angina, both in monotherapy and in combination treatment. The choice of drug, however, remains difficult due to the fact that no one class has been shown to be convincingly superior to the other, while individual patient response may vary.

Drugs in each of these classes reduce pre- and afterload on the heart and can improve coronary blood flow, which corrects the imbalance between myocardial oxygen delivery and demand. Although monotherapy may be effective in some cases, in most patients the use of two or more antianginal drugs is required to eliminate symptoms.

Nitrates. Nitrates do not require special recommendations and are well studied. According to the ACC/AHA 2002 Guideline Update for the Management of Patients With Chronic Stable Angina. Management of stable angina pectoris. Recommendations of the Task Force of the European Society of Cardiology, 1997 ) prolonged nitrates belong to class I drugs.

Although nitrates do not reduce the incidence of complications and mortality in patients with coronary artery disease, they are highly effective both in relieving an attack of angina (nitroglycerin sublingually or in the form of a spray) and in its prevention. If little has been said and written about them recently, this does not mean that these drugs are rarely used in clinical practice - the frequency of their use in the prevention of angina pectoris in various randomized and epidemiological studies varies from 40 to 60%. The frequency of long-term use of nitrates in the EUROPA study (2003) in 12,218 patients was 42.8%, in the Euro Heart Survey ACS (2002) study, out of 10,484 patients, 64.8% regularly took nitrates after myocardial infarction.

The main problems in the prophylactic use of nitrates for angina are: choice of drug, development of tolerance and the occurrence of headaches. For long-term treatment of angina, mononitrates are usually used. These drugs are active metabolites of isosorbide dinitrate, however, unlike it, they are much better absorbed when taken orally, do not undergo biotransformation in the liver and have 100% bioavailability, which provides a predictable concentration of isosorbide mononitrate in the blood plasma and a predictable therapeutic effect, since no changes are required in dosages for liver dysfunction. Currently, the recommended doses are 40 mg and 60 mg; the dose may be increased to 240 mg for retard forms of mononitrates. To achieve an effect, it is extremely important to use nitrates in effective doses; for the retard form of mononitrate, a dose of 40 mg per day is clinically effective with a single use. Single-use mononitrates are more effective, provide a sufficient drug-free period to prevent the onset of tolerance, and are significantly less likely to cause the development of headaches (SONDA, 1995).

How important this is is shown by the latest COMPASS study (2004), in which treatment with mononitrate at a dose of 60 mg per day was significantly more effective and better tolerated by patients than the use of nitrates 2 times a day. Due to these data, the administration of nitrates 3 times a day seems doubtful.

Other drugs of this class are not used in practical medicine due to complete ineffectiveness (nitroglycerin depot preparations) or due to low efficiency (isosorbide dinitrate). Regular use of transdermal drugs is limited due to the development of tolerance to their hemodynamic and antianginal effect.

Antagonists Sa. There has been a decrease in the importance of this class of antianginal drugs. Initially, caution regarding them in the treatment of coronary artery disease was associated with the use of short-acting drugs in the form of monotherapy, as they increase the incidence of coronary complications and mortality.

However, despite the use of long-acting forms, a large number of studies and meta-analyses, the position regarding Ca antagonists remains unchanged - these are drugs of the second or third plan in the treatment of patients with angina pectoris who do not respond to treatment with beta-blockers and nitrates, the third or fourth plan - in the treatment Hypertension that does not respond to diuretics, β-blockers, ACE inhibitors or angiotensin receptor blockers (Psaty B., Furberg C. 2004).

The authors of this commentary also note: if we consider the fact that long-acting dihydropyridines are as safe as placebo, there is no data that would allow us to say how effective they are than placebo in reducing the incidence of complications and death, since they do not add anything to the treatment of patients with stable angina pectoris already receiving standard therapy with beta-blockers, aspirin, nitrates and statins (ACTION, 2004).

Therefore, at present, the place of non-dihydropyridine Ca antagonists in the treatment of angina is to replace β-blockers in the presence of contraindications to their use or the occurrence of side effects during their use; dihydropyridine antagonists are the second drug when monotherapy with β-blockers is ineffective.

Other drugs. Metabolic drugs are not class 1 drugs. According to the recommendations of the European Society of Cardiology, they are assigned an auxiliary role in the treatment of angina pectoris, as they are added to the main antianginal drugs.

Long-term observation of patients with angina pectoris. IHD is a chronic incurable disease that requires constant monitoring. The fate of the patient depends on the quality of this control. According to the ACC/AHA recommendations, the patient should be examined every 4-6 months during the first year after diagnosis of angina. Then examinations should be carried out once a year when the patient’s condition is stable or urgently when angina symptoms worsen or signs of other pathology appear.

At each meeting, a patient with angina needs to receive an answer to the following 5 questions.

1. Has your level of physical activity decreased since your last visit?
2. Has the frequency or severity of angina increased? If this occurs or the patient reduces the level of physical activity to avoid provoking angina, treatment should follow the principles of treatment of unstable angina.
3. How does the patient tolerate the treatment?
4. Are there advances in addressing risk factors (especially hypertension, diabetes, and hyperlipidemia)?
5. Has the patient developed a new disease over the past period and does the concomitant pathology affect angina pectoris?

What examinations should be performed when monitoring a patient with angina pectoris?

1. Repeated ECG when using drugs that can affect conductivity when the nature of the pain syndrome changes, palpitations or interruptions in cardiac activity.
2. Radiography of a patient when clinical HF occurs or its aggravation.
3. EchoCG with determination of EF and segmental contractility in the event of clinical HF or its aggravation.
4. ECG - stress testing in patients with a changed pain syndrome in the absence of ECG abnormalities (WPW syndrome, ST depression more than 1 mm at rest or complete blockade of the LBP).
5. If there are ECG abnormalities specified in paragraph 4, radionuclide testing is performed. With a history of revascularization, as well as questionable ECG testing data.
6. Coronary angiography in patients with angina pectoris class 3 despite maximum drug therapy.