Federal Guidelines for the Use of Medicines

The publication contains recommendations based on evidence-based medicine data on the use of drugs in the treatment of the most common diseases, as well as basic information about drugs of domestic and foreign production (trade names, indications and contraindications, side effects, release forms, etc.).

Designed for a wide range of doctors, pharmaceutical workers, medical students.

Official sources of information on medicinal products (MP), in which the entire information base is spelled out are: pharmacopoeial monograph, clinical and pharmacological article (typical clinical and pharmacological article of drugs and clinical and pharmacological article of drugs), drug passport, State Register of Medicines of the Russian Federation. The source of information about medicines are instructions for the use of the drug, the List of vital medicines (general and in the main areas: pediatrics, cardiology, etc.), the Federal guidelines for the use of medicines (formulary system), as well as scientific articles, reference books, textbooks , the Internet,

principles of rational pharmacotherapy

Pharmacotherapy - a section of pharmacology that studies the patient's drug therapy.

For the rational choice of drugs, there are four criteria developed by the World Health Organization (WHO), according to which both whole pharmacological groups and individual drugs are assessed:

· Efficiency

· Safety

· Acceptability

· The cost

1. The number of drugs used should be limited to the minimum necessary; it is undesirable to prescribe more than three drugs simultaneously on an outpatient basis.

2. When combining drugs synergists, the dose of each of them is reduced by 1.52 times.

3. It is desirable to simplify the medication regimen as much as possible, giving preference to long-acting drugs.

4. If long-term therapy is necessary, the ratio of the “cost-effectiveness” of drugs and the patient's financial capabilities should be taken into account.

5. It is necessary to inform the patient about the goals and duration of treatment, the expected results, the principle of action of the prescribed drugs, to warn about possible side effects and their recognition. drug interactions with alcohol, effects on driving, etc. You should discuss in detail (and write down!) The regimen of taking medications, indicate the time and method of taking the medication, the patient's actions in case of forced or accidental admission.

6. You should strive to ensure that the desired therapeutic effect is provided by the lowest effective dose of the drug.

7. Dosing tactics (gradual increase of the dose. Shock with the transition to maintenance doses, stable maintenance dose, gradual dose reduction, etc.) depends on the specificity of the drug used and the clinical situation.

9. Adequate assessment of the results of dose adjustment is possible no earlier than after 4 half-life of the drug, provided that it is taken regularly (it is also necessary to amend the timing of the development of the pharmacological effect).

10. Cancellation of some medications should be performed gradually (corticosteroids, beta-blockers, clofellip, H2 blockers). It is necessary to warn the patient about this.

11. It is necessary to form a patient's high adherence to the prescribed treatment.

12. In the absence of the expected effect, the possible causes should be analyzed.

Federal Law "On the Circulation of Medicines" dated 12.04.2010 N 61-FZ (current edition, 2016)

1. This Federal Law regulates relations arising in connection with circulation - development, preclinical studies, clinical trials, expertise, state registration, standardization and quality control, production, manufacturing, storage, transportation, import into the territory of the Russian Federation, export from the territory of the Russian Federation, advertising, dispensing, selling, transferring, using, destroying medicines.

Methods for high-precision delivery of drugs into the body. Nanoparticles used to deliver therapeutic molecules (fullerenes, dendrimers, nanotubes, liposomes, nanoclusters).

Nanotechnology is a field of scientific knowledge aimed at solving technological problems associated with the manipulation of matter (atoms and molecules) in the range from 1 to 100 nanometers. When the size of the object under study is reduced to scales of 100 nm or less, the classical physical laws of interaction between atoms and molecules are replaced by quantum ones, for example, tunneling transitions and surface plasma resonance (SPR). A system with dimensions in the nanometer range can be described from the standpoint of thermodynamics of nonlinear processes. The total effect of nanotechnology in pharmacology is a fundamentally new approach, which consists of the following components:

1.medicines are used in doses that are significantly less than the known pharmacopoeial ones;

2. the drug is packaged or bound to the membrane of the nanostructure and in this form reaches the target organ;

3. the metabolic transformation of the drug slows down, and it has a longer and stronger effect in the patient's body;

4. the degradation of the nanostructure does not occur immediately, but within a certain time, and its effect is summed up;

5. the nanostructure, in itself, has biological activity, since the size and charge of the nanostructure (liposomes, fullerenes and others) affect the bond energy and interaction with cellular and molecular structures;

6. Pharmacokinetic parameters for each specific drug packaged in nanostructures vary significantly.

Drug delivery systems (DDS) - a liposome equipped with a "molecular compass" (antibodies that help find the affected organ) reflect nanotechnology approaches. Delivery of drugs using monoclonal antibodies for addressing drug delivery can significantly improve the quality of life of patients by reducing side effects, as well as increase the selectivity, and hence the effectiveness of treatment. Nanotechnology makes it possible to carry out microscopically precise operations for the destruction of pathological foci. To do this, metal nanoparticles with drugs and antibodies fixed on them are injected into the body. With the help of specific antibodies, nanostructures that play the role of a "molecular compass" unmistakably identify targets for affecting pathologically altered cells, attach to them due to the antigen-antibody reaction and destroy them using a transported drug (antiblastoma antibiotics). Nano-neuropharmacology involves the use of drugs in new dosage forms - nanostructures of neurotropic action, which have the properties of correcting the function of the central nervous system (liposomes, fullerenes, dendrimers, nanoclusters, nanotubes, and others). A technique for the biochemical synthesis of metal nanoparticles (Ag, Au, Cu, Zn, Co, Ni and others) has been developed. Standardized nanoparticles (15 nm) retain their stability in air for a long time and can be used in micellar and aqueous solutions. At the same time, they acquire high antimicrobial, catalytic and other useful properties.

Pathological changes in the osteoarticular apparatus arose even in our distant ancestors. And modern medicine gives disappointing facts: more than half of the population of our country (over 65) suffer from joint diseases; one of them - arthrosis - does not affect only 3% of elderly people, the rest are faced with its manifestations. Rheumatoid arthritis after 5 years from the beginning of its development leads to disability. The main reason for this phenomenon is the lack of adequate treatment, therefore an international protocol for the treatment of chronic joint diseases was developed.

Pain as a constant companion of life

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

Research shows a sad picture:

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

Acute pain becomes the cause of the development of functional impairment of the joint already in the early stages of the disease. It plunges a person into a state of constant emotional stress, anxiety and even depression, which, in turn, leads to cardiovascular disorders. Therefore, the elimination of pain is the primary task of treating polyarthritis of any origin.

Official standards of pharmacotherapy

The first problem to be solved by the links of the chain of correctly selected therapy is pain relief. In traditional pharmacological practice, analgesics and non-steroidal anti-inflammatory drugs are used for this purpose.

The first link: anti-inflammatory therapy

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

• diclofenac;
• indomethacin;
• piroxicam;
• ibuprofen.

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

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

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

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

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

However, many attending physicians persist in treating arthritis with drugs from another group of NSAIDs, adhering to outdated treatment standards. In addition, there are unfounded assumptions about the negative effect of selective COX 2 inhibitors on the state of the cardiovascular system and their ability to cause liver dysfunction. Recent research has proven the inconsistency of such claims.

The main representatives of this group of drugs:

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

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

Second link: analgesics

European and domestic rheumatologists adhere to the point of view that the main drug for the treatment of polyarthritis should be precisely the anesthetic, and the course of taking NSAIDs should fade into the background and be as short as possible. But taking into account the fact that polyarthritis is a long-term current disease, which is accompanied by constant inflammation of the articular elements, many experts still take non-steroidal anti-inflammatory drugs to the 1st place.

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

Third link: chondroprotectors

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

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

The main medicines of this group:

• teraflex (complex preparation);
• chondroitin sulfate;
• don (glucosamine-based monopreparation);
• arthra.

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

The fourth link: muscle relaxants

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

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

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

Relaxants of the central type of action are mainly used: sirdalud, midocalm, baclofen, tranxen, diazepam. All of them have a wide range of side effects: they cause drowsiness, muscle weakness, dry mouth, and lower blood pressure. The mildest drugs are sirdalud and midocalm.

Folk remedies as an adjunct to the main treatment

Traditional medicine offers a wide variety of treatments for arthritis. The most effective of them are the means of api and herbal medicine.

Treatment with compresses or rubbing with various alcoholic tinctures is popular among patients with polyarthritis. This is a really good way to relieve pain and somewhat reduce inflammation, but it must be remembered that traditional medicine still cannot offer an effective pathogenetic treatment for polyarthritis. Therefore, its methods can only be used in conjunction with a traditional treatment regimen.

It should not be forgotten that traditional medicine often uses herbal products. And modern environmental conditions make one deeply doubt its quality and safety of the active ingredients.

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

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. to ensure in certain clinical situations the successful solution of the assigned treatment tasks. The strategic goals of pharmacotherapy can be different: cure (in the traditional sense), slowing the development or arresting an exacerbation, preventing the development of the disease (and its complications), or eliminating painful or prognostic adverse symptoms. In chronic diseases, medical science has determined the main goal of treating patients to control the disease with a good quality of life (i.e., subjectively good condition of the patient, physical mobility, absence of pain and discomfort, ability to serve oneself, social activity).

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

Physical mobility;

Lack of pain and discomfort;

The ability to serve oneself;

Ability for normal social activity.

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

Drug risk has become a major medical concern over the past 40 years. This concern intensified after the thalidomide disaster in 1960-61, when, after taking it by pregnant women, children were born who horrified the world with their ugliness. This was an extremely dramatic example from the whole 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 development of the disease).

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

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

5. General strengthening (restoration of disturbed links of the adaptive system of the body).

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

In acute illness, most often, treatment begins with etiotropic or pathogenetic pharmacotherapy. With an 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 sex of the patient, the state of his compensatory systems, in most cases, treatment includes all types of pharmacotherapy.

Before starting pharmacotherapy, you should determine the need for it.

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 unavoidable (for example, the need for emergency surgery).

One of the most important principles of clinical pharmacology is to prescribe a medicine when there is an indication for it.

The appointment "just in case" of B vitamins, which show allergenic properties in a number of people, increases the number of anaphylactic reactions.

Elevated temperature is a protective reaction of the body, and in the overwhelming number of cases at temperatures below 38 C, the appointment of antipyretics is not required.

Routine prescription of antibiotics for viral diseases from the first day of illness in order to “prevent secondary infection” has become the "talk of the town".

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

At the same time, it is worth paying attention to the reputation of the company that produces drugs, since the same drugs produced by different companies can have serious qualitative differences.

27.03.2015

How important is angina?
Angina pectoris is the most common manifestation of ischemic heart disease (CHD) in our country. According to statistics for 2003, angina pectoris was detected in 2,720,000 inhabitants of Ukraine, which is 37% of all cases of diagnosed coronary artery disease (7,272,619) and 40% of all cases of newly diagnosed coronary artery disease (258,337).
This corresponds to the data obtained in the UK, where analysis of 295 584 cases of newly diagnosed coronary artery disease found that exertional angina is the most frequent first manifestation of coronary artery disease - 46%, MI - 27%, sudden death - 14% and unstable angina - 13% (Sutcliffe S. et al., 2003). At the same time, the average incidence of angina pectoris per year is 213 per 100,000 of the population over 30 years old (Elveback L. et al., 1986).
The prevalence of angina pectoris in Ukraine compared to 1999 increased by 64% and approximately
2 times higher (5.7% of the population) than in the United States (3.8% of the population). At the same time, mortality from coronary heart disease in the structure of all causes of death in Ukraine is also
2 times higher than the average European indicators and US statistics (41%, 22% and 20%, respectively; British Heart Foundation. European Cardiovascular Disease Statistics 2000).

Consequences of angina pectoris. The occurrence of angina pectoris leads not only to a deterioration in the quality of life (a decrease in the tolerance of physical and psycho-emotional stress), but also increases the risk of unstable angina pectoris and the development of MI by 3 times, which means that it leads to an increase in the risk of death. During the first year after the onset of angina pectoris, 10% of patients develop myocardial infarction or die, 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 examination, for 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, 635,000 patients with angina pectoris had 2.35 million doctor visits, 16 million prescriptions, 149,000 hospitalizations, 117,000 angiographies, 21,400 CABGs and 17,700 PTCA (Stewart S., Eur. Heart J. 2002, 4, 720).
If angina pectoris is not diagnosed in a timely manner, this will lead to the fact that the patient will not receive adequate treatment that could improve the quality and duration of his life. The consequence will be the progression of symptoms and the development of complications (MI or death) in those at high risk. IHD is the cause of death of approximately every second inhabitant of our country.
Problems of pharmacological treatment of angina pectoris. The following traditional and interrelated problems of angina pectoris can be distinguished: poor-quality diagnosis and inadequate treatment. Poor diagnostics can lead to the labeling of angina pectoris and, as a result, to the appointment of unnecessary treatment, an increase in the level of neurotization, unnecessary additional examination and hospitalization, as well as to the lack of effect of treatment.
The specific problems of the pharmacological treatment of angina pectoris are as follows.
1. Treatment of atypical pain syndrome as classic angina pectoris (the diagnosis has not been verified).
2. Insufficient treatment:
- low doses of antianginal drugs;
- lack of control over heart rate during treatment with β-blockers.
3. Polypharmacy (many unnecessary drugs).
4. Risk factors are not identified and corrected.
Purpose of treatment for stable angina. When starting the treatment of patients with stable angina, it is necessary to clearly understand that there are only two goals for treating patients with such a diagnosis. The first is the prevention of MI and death, which means the extension of life. The second is a decrease 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 case when there are two different methods of treatment (drug) 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 presupposes, on the one hand, an accurate diagnosis of stable angina pectoris, and on the other, the determination of the degree of risk of complications. The choice of the correct treatment depends on this, since it is different depending on the goal.
A prerequisite for effective treatment is also a good knowledge of the patient with the essence of their disease and understanding of the meaning of treatment. For most patients, the goal of treatment should be complete or almost complete elimination of anginal pain and return to normal life and functional abilities corresponding to functional class I of angina pectoris. 82% of patients with stable exertional angina limit daily activities in order to avoid angina attacks, and seek to increase sleep and rest time. (Chestnut L. G. et al., Measuring Heart Patients' Willingness to Pay for Changes in Angina Symptoms: Some Methodologocal 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 ensure that only limited exercise is performed.
Sometimes it is quite difficult to assess such a subjective indicator as the quality of life and often there is a discrepancy between the opinion of the doctor and the patient. The doctor may believe that the prescribed treatment controls the attacks of angina pectoris, while the patient is confident in the opposite. In a UK study of 5,125 patients with angina, half of the patients reported two or more attacks per week, but 62% of the patients described their health as “unsatisfactory” or “poor” (Pepine CJ 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 stable angina, the newer American Heart Association (ACC / AHA, 2002), and the newer, American College of Physicians (ACP, 2004). In the spring of 2005, the emergence of new recommendations for the treatment of stable angina pectoris of the European Society of Cardiology was announced, since it is clear that the current ESC recommendations are already significantly outdated.
The year 2004 also brought new recommendations of the European Society of Cardiology on the use of the main classes of pharmacological drugs that are used in the treatment of stable angina pectoris.

Medication for angina pectoris to prevent MI and death
Antiplatelet drugs. The growing importance of antithrombotic drugs has led to the publication of separately developed recommendations of the European Society of Cardiology on their use (Patrono C. et al., 2004). Drugs of this class should be prescribed routinely and for a long time to all patients with a diagnosis of coronary artery disease, even in the case when 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 is growing - the only antiplatelet drug proven to be better than aspirin in the prevention of MI, stroke and vascular death. The combination of aspirin and clopidogrel leads to an even greater increase in the effectiveness of treatment. There is a need for this in the case 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 in coronary artery disease both as monotherapy and 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 frequency of recurrent myocardial infarctions and symptoms of ischemia. Diabetes mellitus is no longer a contraindication to the prescription of β-blockers - their effectiveness in these patients is even higher. In the recommendations of the European Society of Cardiology, β-blockers are recommended as an initial treatment in the absence of contraindications, especially in patients with myocardial infarction, since 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 can lead to symptomatic bradycardia or a higher degree of blockade. 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 low doses.
The higher the patient's heart rate at rest, the higher the effectiveness of β-blockers. A decrease in heart rate during treatment can reach 55 per minute, subject to good tolerance and the absence of symptomatic hypotension. Preparations without intrinsic sympathomimetic activity are preferred. The main principle of using β-blockers is to prescribe them in doses that provide a distinct effect of blocking β-adrenergic receptors. To do this, it is necessary to achieve a decrease in heart rate at rest to 55-60 per minute, which is not always achieved in real clinical practice and is accompanied by insufficiently pronounced
effect.
Lipid-lowering drugs... Statins should be prescribed to all patients with coronary artery disease. The question remains, what should be the target level of LDL reduction? Until now, this level has been less than 100 mg / dL.
However, in 2004, revolutionary changes took place in the field of lipid-lowering therapy. Based on the results of the latest studies of HPS and PROVE IT, in a specially issued supplement to the generally recognized recommendations of NCEP ATP III in the group of high-risk patients (diabetes mellitus, metabolic syndrome, smokers, after acute coronary syndrome), a new target level of LDL reduction is recommended - less than 70 mg / dl (Grundy S. et al., 2004).
Currently, all statins at our disposal have randomized trials with "hard endpoints" and can be used in patients with angina pectoris. Simvastatin, pravastatin and atorvastatin have the greatest evidence base on the effectiveness and safety of treatment.
ACE inhibitors. The recently published consensus of experts 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, efficacy in reducing mortality has been proven only for tissue ACE inhibitors ramipril and perindopril. Only for these drugs the theoretical premises and experimental data have been confirmed in large randomized controlled trials HOPE and EUROPA. The research results are so convincing that it was on their basis that a new indication for the prescription of ACE inhibitors was added - the secondary prevention of cardiovascular diseases without heart failure or left ventricular dysfunction (ESC, 2004). And in October 2004, the American College of Physicians (ACP), based on these studies, recommended the use of ACE inhibitors for all patients with stable angina pectoris, asymptomatic suspected or established coronary artery disease.

The 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 when all four drug classes are used concurrently. With such a complex treatment, the greatest possible degree of reduction in the risk of IHD complications and death is achieved at present.

Medical treatment of angina pectoris, aimed at eliminating symptoms. In the treatment of angina pectoris, three classes of antianginal drugs are used: β-blockers, prolonged Ca antagonists and nitrates, prolonged and short-acting (to stop an attack of angina pectoris). All of these classes of drugs have been shown to be effective in reducing the incidence of angina pectoris, both in monotherapy and in combination therapy. The choice of drug, however, remains a difficult task due to the fact that no one class has been shown to be convincingly superior to another, while the individual patient's response may vary.
Drugs in each of these classes reduce pre- and afterload on the heart and can improve coronary blood flow, which removes the imbalance between myocardial oxygen delivery and demand. Although monotherapy can be effective in some cases, most patients require two or more antianginal drugs to eliminate symptoms.
Nitrates. Nitrates do not need any special recommendations and are well studied. According to the American and European Society of Cardiology's Guidelines 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-release nitrates are 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 stopping an attack of angina pectoris (nitroglycerin sublingual or in the form of a spray), and in its prevention. If in recent years little has been said and written about them, 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 intake of nitrates in the EUROPA (2003) study in 12,218 patients was 42.8%, in the Euro Heart Survey ACS (2002), out of 10,484 patients, 64.8% regularly took nitrates after a myocardial infarction.
The main problems in the prophylactic use of nitrates for angina pectoris are: the choice of the drug, the development of tolerance and the occurrence of headache. For long-term treatment of angina pectoris, 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 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, it is possible to increase the dose to 240 mg for retard forms of mononitrates. To achieve the 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 in a single application. Single-dose mononitrates are more effective, provide a sufficient drug-free period to prevent the onset of tolerance, and are significantly less likely to cause 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 twice a day. Due to these data, the appointment of nitrates 3 times a day seems doubtful.
Other drugs of this class are not used in practical medicine due to complete ineffectiveness (depot nitroglycerin preparations) or due to low efficiency (isosorbide dinitrate). The constant intake of transdermal drugs is limited due to the development of tolerance to their hemodynamic and antianginal effects.
Ca antagonists. There is a decrease in the value of this class of antianginal drugs. Initially, suspicion in relation to 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 prolonged forms, a large number of studies and meta-analyzes, 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 β-blockers and nitrates, of 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 comment also note that if it is considered proven that prolonged-release dihydropyridines are as safe as placebos, there is no data that would suggest how much they are more effective 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 β-blockers, aspirin, nitrates and statins (ACTION, 2004).
Therefore, at present, the place of non-dihydropyridine Ca antagonists in the treatment of angina pectoris is the replacement of β-blockers in the presence of contraindications to their appointment or the occurrence of side effects during their use, dihydropyridine is the second drug when monotherapy with β-blockers is ineffective.
Other drugs. Metabolic drugs are not class I drugs. According to the recommendations of the European Society of Cardiology, they are assigned an auxiliary role in the treatment of angina pectoris, since they are added to the main antianginal drugs.
Long-term observation of a patient 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 / ANA recommendations, the patient should be examined every 4-6 months during the first year after the diagnosis of angina pectoris. Then examinations should be carried out once a year when the patient's condition is stable or urgently when the symptoms of angina pectoris worsen or signs of another pathology appear.
At each meeting, a patient with angina pectoris needs to get 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 pectoris increased? If this happens or the patient has reduced the level of physical activity in order not to provoke angina pectoris, treatment should be in accordance with the principles of treatment of unstable angina.
3. How does the patient tolerate the treatment?
4. Are there any successes in eliminating risk factors (especially arterial hypertension, diabetes mellitus 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 carried out when observing a patient with angina pectoris?
1. Repeated ECG when using drugs that can affect conduction when the nature of the pain syndrome changes, palpitations or interruptions in the activity of the heart.
2. Radiography in a patient with the occurrence of a heart failure clinic or its aggravation.
3. Echocardiography with the definition of EF and segmental contractility in the event of a heart failure clinic or its aggravation.
4. ECG - stress testing in patients with altered pain syndrome in the absence of ECG abnormalities (WPW syndrome, ST depression of more than 1 mm at rest, or complete blockade of LDBH).
5. In the presence of ECG abnormalities specified in paragraph 4 - radionuclide testing. With a history of revascularization, as well as questionable ECG testing data.
6. Coronary angiography in patients with 3 FC angina pectoris in spite of maximum drug therapy.

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Pharmacotherapy is a rapidly developing area of \u200b\u200bclinical medicine. Specialists in the field of modern pharmacotherapy are developing a scientific system for the use of drugs. Pharmacotherapy is classified as a synthetic discipline, it is based mainly on modern methods of clinical diagnostics, evidence-based medicine methodology and clinical pharmacology.

10.1. TYPES OF PHARMACOTHERAPY

There are several types of pharmacotherapy:

Etiotropic (aimed at eradicating the cause of the disease);

Pathogenetic (affects the development of the disease);

Substitutional (injected drugs compensate for vital substrates, the synthesis of which is difficult or absent in the body);

Symptomatic (blocks certain syndromes or symptoms that aggravate the patient's life);

General strengthening (aimed at restoring disturbed links of the body's adaptive system);

Preventive (aimed at preventing the development of an acute process or lengthening remission).

If the development of the disease was acute, etiological or pathogenetic pharmacotherapy is performed. With an exacerbation of chronic diseases, the choice of pharmacotherapy depends on the severity and localization of the process, age and sex, the state of compensatory systems, and in most cases includes all types of pharmacotherapy.

All types of treatment can use medicinal technologies presented by clinical pharmacology from different positions.

The successes of pharmacotherapy of the last decade are closely related to the development of the principles and technologies of "evidence-based medicine", on the basis of which justified pharmacotherapy is regulated. The results of these studies contribute to the introduction into clinical practice of new technologies aimed at slowing the development of the disease and delaying severe and fatal complications (β-blockers and spironolactone in the treatment of CHF, the use of inhalation

glucocorticoids in bronchial asthma, ACE inhibitors in diabetes mellitus, etc.). The indications for long-term and even life-long use of drugs, which are based on evidence-based medicine, have expanded.

The connection between clinical pharmacology and pharmacotherapy is so close that it is sometimes difficult to draw a line between them, since they are based on general principles, set common goals and objectives for themselves - effective, competent, safe, rational, individualized and economical therapy. A specialist in the field of pharmacotherapy determines the strategy and forms the goal of treatment, and in the field of clinical pharmacology - provides tactics and technology to achieve this goal.

10.2. GOALS AND OBJECTIVES OF RATIONAL PHARMACOTHERAPY

The main elements of tactics and technology of rational pharmacotherapy in a particular patient include solving the following tasks:

Determination of indications for pharmacotherapy;

The choice of a drug or a combination of drugs;

Choice of routes and methods of administration, dosage forms;

Determination of the individual dose and dosage regimen of drugs;

Correction of drug dosage regimens in the course of pharmacotherapy;

Selection of criteria, methods, means and timing of pharmacotherapy control;

Justification of the timing and duration of pharmacotherapy;

Determination of indications and technologies for drug withdrawal. The primary question that arises when prescribing treatment is

the need to use drugs in a particular patient. After establishing such a need, prescribing drugs is possible if the likelihood of a therapeutic effect exceeds the likelihood of undesirable consequences associated with its use.

The principle of rationality underlies the construction of pharmacotherapy tactics in a specific clinical situation, the analysis of which makes it possible to substantiate the choice of the most appropriate drugs, dosage forms, doses and routes of drug administration, as well as the expected duration of pharmacotherapy. The duration of pharmacotherapy is determined taking into account not only the expected dynamics of the disease, but also the expected dynamics of the pharmacological effect and the possibility of the formation of various types of drug dependence.

Pharmacotherapy is not indicated if the disease is not painful for the patient and the predicted outcome of the disease does not depend on the use of drugs, and also when non-drug treatments are more successful, being safe, or have advantages or are unavoidable (for example, the need for emergency surgery).

The goals and objectives of pharmacotherapy are largely determined by the type of pharmacotherapy and may be different. For example, the goal and task of pharmacotherapy for symptomatic treatment in an acute situation are usually the same - removal of painful symptoms, sensations, mental discomfort, relief of pain, fever reduction, etc. In pathogenetic therapy, depending on the nature of the course of the disease (acute or chronic ), the tasks of pharmacotherapy can differ significantly and determine different technologies for the use of drugs.

So, in case of a hypertensive crisis, the task of quickly eliminating the symptoms of a hypertensive crisis, reducing the risk of consequences and complications of falling blood pressure to the required level should be solved. In this situation, a drug or a combination of drugs is used in the technology of a pharmacological test. With prolonged high and persistent arterial hypertension, a stepwise decrease in blood pressure is performed. In this case, pathogenetic therapy solves both the immediate goals (elimination of the symptoms of the disease) and the strategic goal of prolonging life, ensuring the quality of life, and reducing the risk of complications of arterial hypertension (stroke, myocardial infarction). In the course of pathogenetic therapy, various technologies are used to provide individualized pharmacotherapy.

10.3. STAGES OF RATIONAL PHARMACOTHERAPY

The tasks of pharmacotherapy are solved in stages.

Making a diagnosis and determining the severity of the patient's condition.

Assessment of the functional state of organs and systems involved in pharmacokinetic and pharmacodynamic processes

The choice of the type of pharmacotherapy for a given patient.

Selecting a group of drugs. They are carried out according to the leading or underlying disease (syndrome), formulate the goals and objectives of the treatment of a particular patient, based on the nosology or syndromes, the severity of the course and severity of the disease, knowledge of the general principles of treatment of this pathology, possible complications, previous drug and non-drug therapy. Accepted in

Attention is the prognosis of the disease, especially the manifestation of the disease in a particular patient. The choice of drugs in accordance with the individual characteristics of pharmacokinetics and pharmacodynamics, observing the following principles:

It is necessary to know enzymes of biotransformation and transporters involved in pharmacokinetic processes

It is necessary to know information about the effect of drugs on biotransformation enzymes and transporters (induction / inhibition);

If the patient took drugs that are inducers / inhibitors of biotransformation enzymes and transporters, it is necessary to assess their activity;

If in the population to which the patient is referred, polymorphism of genes encoding biotransformation enzymes and transporters occurs in more than 5%, then there is a need for pharmacogenetic testing.

Starting treatment, the doctor must predict a strategic result, determine the required level of restoration of functional disorders at various stages of treatment: removal from an acute state, stabilization of the state, etc. In other words, the doctor must specify the value of the desired effect. For example, in a hypertensive crisis in a patient with a first-ever increase in blood pressure, the desired effect is the normalization of blood pressure within 30-60 minutes. In a hypertensive crisis in a patient with stable arterial hypertension, the magnitude of the desired effect is to lower blood pressure to the numbers to which the patient is adapted, since a sharp decrease in blood pressure in such a patient can lead to complications (ischemic stroke). To remove the patient from acute pulmonary edema, it is necessary to obtain a diuresis of about 1 liter per hour when using diuretics. When treating diseases of the subacute and chronic course, the desired result may be different at different stages of treatment.

It is more difficult to specify and select control parameters when carrying out therapy with drugs of metabolic type. In these cases, the assessment of drug action can be carried out indirectly using evidence-based medicine or meta-analysis techniques. In order to prove the efficacy of trimetazidine in the treatment of coronary artery disease, it was necessary to conduct a multicenter prospective study and evaluate the feasibility of using this drug (a decrease in the incidence of coronary heart disease complications in the study group compared to the control group).

Formed at the 1st, 2nd and 3rd stages, the goals and objectives of treatment largely depend on the psychological characteristics of the patient, the degree of his trust in the doctor, his adherence to treatment. Based on the characteristics of the course of the disease (syndrome), the degree of dysfunction in the patient, the main pathophysiological links in the development of the disease, the putative targets and mechanisms of drug action are also determined. In other words, the spectrum of pharmacodynamic effects of drugs necessary for the patient is distinguished. The desired (or necessary) pharmacokinetic characteristics of the drug and the required dosage form are determined. Thus, a model of the optimal drug for a particular patient is obtained.

At the 4th stage, the doctor chooses the pharmacological group or groups of drugs that have the necessary set (spectrum) of pharmacodynamic effects. At the 5th stage, drugs within the group are selected taking into account the data on pharmacokinetics and pharmacodynamics. Also at the 5th stage, the doses of the selected drug, the frequency of administration and methods of monitoring the effectiveness and safety in relation to a particular patient are determined. The selected drug must match (or approach) the optimal drug.

10.4. PHARMACOLOGICAL ANAMNESIS

At the 2nd and 3rd stages of pharmacotherapy, a carefully and purposefully collected pharmacological history is essential for decision-making. Its value in choosing a drug can be compared with the value of the medical history for the diagnosis. This information allows you to avoid mistakes in the presence of drug intolerance (allergic, toxic reactions), to get an idea of \u200b\u200bthe effectiveness or lack of effect of previously used drugs. In some cases, it is possible to identify the reason for the low efficiency or side effects of the drugs used - a low dose, violation of the rules for taking drugs, etc.

In one clinical observation, undesirable drug reactions (nausea, vomiting, dizziness, anxiety) when a patient was using a prolonged theophylline preparation at a dose of 300 mg were caused by the fact that the patient, unable to swallow the tablets, thoroughly chewed them and washed them down with water. This changed the kinetics of the prolonged form of the drug, led to a high peak concentration of drugs in the blood serum and to the development of undesirable drug reactions characteristic of theophylline. Having from the patient ta-

any information, there is no need to give up this drug. It should be used in a smaller dose and in a different dosage form.

The information obtained during the collection of the pharmacological history can significantly affect the choice of the primary drug or its initial dose, and change the tactics of drug therapy. For example, an indication in the history of the lack of effect when using enalapril at a dose of 5 mg for arterial hypertension in a patient with type II diabetes mellitus may allow linking the lack of effect with a low dose of the drug. An indication in the history of the escape of the diuretic effect in a patient with CHF with prolonged use of furosemide will change the treatment tactics and determine the indications for combination therapy: the addition of spironolactone, other potassium-sparing diuretics or potassium preparations (depending on the causes of tolerance to furosemide). The lack of effect of treatment with inhaled glucocorticoid hormones in a patient with bronchial asthma may in fact be the result of a violation of the inhalation technique.

10.5. CHOICE OF MEDICINAL PRODUCT AND DOSING MODE

In recent years, treatment is often started with regulated drugs. Regulated first-line drugs for many common diseases are well known. The drugs of the first choice are included in the state list of vital drugs, are indicated in the formulary of the medical institution and are proposed in the approved standard treatment regimens for the category of patients under consideration.

If a certain optimal drug approaches in its pharmacodynamic effects and pharmacokinetic parameters to the regulated drug, then the latter can become the drug of the first choice.

Stage 3 of pharmacotherapy is quite difficult, and there are various options for solving its problems. So, if a history of intolerance or a reliable lack of effect is indicated when using a regulated drug, another drug is selected that corresponds to the optimal drug. It may also turn out to be a regulated drug, or in a specific clinical situation there may be a need for a non-standard decision regarding the prescription of drugs.

Having chosen a drug, it is necessary to clarify information about the beginning, the period of maximum action, pharmacodynamic effects, both main and undesirable, it is imperative to correlate the risk of developing undesirable drug effects with concomitant diseases and syndromes in a particular patient, and sometimes, admitting his mistake, already at this stage refuse from the use of such drugs. For example, if there are all indications for the use of nitrates in a patient, it is necessary to abandon their use in a patient with glaucoma or if the patient has intracranial hypertension.

Taking into account the purpose and depending on the duration of the action of the administered drug, a one-time daily dose is determined, and sometimes a course dose.

When determining a single dose, the criterion for its adequacy is the required therapeutic effect in the expected duration of the drug's action after its single use.

Treatment begins with a regulated average dose, which provides the therapeutic concentration of drugs in the body for the chosen route of administration, and the recommended dosage regimen of drugs. An individual dose is defined as the deviation from the average dose required for a particular case. The need to reduce the dose arises due to age-related characteristics, in violation of the drug elimination systems, in violation of homeostasis, increased sensitivity or limited number of receptors in organs, targets (for example, for cardiac glycosides in myocarditis), in case of hypersensitivity of the patient to this drug, at risk the occurrence of cross-allergic reactions.

Higher doses are required when the bioavailability of the drug decreases, the patient has low sensitivity to it, as well as when drugs with competitive properties and drugs that accelerate the metabolism or excretion of the drug are used.

An individual drug dose may differ significantly from the average dose indicated in reference books and manuals. In the process of using drugs, the dose is adjusted according to the observed effect, it can be changed depending on the patient's condition and the total amount of pharmacotherapy.

Doses of drugs with the ability to material and functional cumulation can be different at the beginning of treatment (initial dose, saturating dose) and during its duration (maintenance dose). For such drugs, initial dosage regimens are being developed that provide for a different rate of onset of the effect depending on the rate of saturation (cardiac glycosides, etc.).

If necessary, the individual drug dose can be changed taking into account the characteristics of the course of the main or concomitant diseases, pharmacological history, degree of dysfunction, predicted individual characteristics of pharmacokinetics.

An individual drug dosage regimen can be developed in accordance with chronopharmacology, which increases the efficacy and safety of pharmacotherapy. Chronopharmacological technology is a preventive chronotherapy, taking into account the time of the onset of the maximum deviation of a particular function from the norm and the pharmacokinetics of drugs. For example, the appointment of enalapril to a patient with arterial hypertension 3-4 hours before the maximum increase in blood pressure (acrophase blood pressure) will increase the effectiveness of antihypertensive therapy. A chronopharmacological approach that takes into account biological rhythms is the basis for prescribing the entire daily dose of systemic glucocorticoids in the morning to reduce the risk of secondary adrenal insufficiency.

10.6. PHARMACOLOGICAL TEST

Evaluation of the patient's individual response to the first use of drugs is called a drug test or pharmacological test. Acute pharmacological test (test) is an important technological technique used in pharmacotherapy to individualize treatment. Its implementation allows you to establish the degree and reversibility of functional disorders, the tolerance of the selected drug, as well as predict the clinical efficacy of many drugs and determine the individual dosage regimen, especially if there is a complete correlation between the first effect of this drug and its subsequent action.

Conducting a test includes dynamic observation of a group of indicators reflecting the functional state of the system that is affected by the selected drug. In the classical version, the study is carried out at rest before meals, possibly with physical or other exertion, followed by its repetition after taking the drug. The duration of the study depends on the pharmacodynamic, pharmacokinetic properties of the drug, as well as on the patient's condition.

Diagnostic medicinal samples have long been used in clinical medicine to clarify the mechanism and degree of dysfunction of the organs or systems under study. For example, a sample with nitroglycerin is widely used in rheovasographic studies.

tests, stress test with potassium - to assess metabolic disorders in the myocardium.

Pharmacological tests are often used in modern functional diagnostics:

Dobutamine stress echocardiography (used to verify the diagnosis of coronary artery disease, as well as to identify viable myocardium in patients with CHF);

Echocardiography with nitroglycerin test (can provide information about the reversibility of restrictive diastolic dysfunction of the left ventricle);

ECG with atropine test (used to distinguish between bradycardia associated with the influence of the vagus nerve and bradycardia caused by organic damage to the myocardium);

Study of the function of external respiration with a test of β 2 -adrenomimetics (used to detect reversible bronchial obstruction).

The pharmacological test is carried out with drugs that have the effect of the "first dose" or a clear relationship between concentration and pharmacological effect. This technology is impractical and is not carried out when using chemotherapeutic drugs (drugs) with a long latency period of pharmacological action.

The structure of the pharmacological test assumes targeted temporary control of the predicted pharmacodynamic effects of drugs, both direct and unwanted drug reactions, using available control methods. The use of drugs in an acute clinical situation is, in fact, a pharmacological test: the doctor evaluates the effectiveness and safety of drugs. For example, intravenous administration of furosemide, along with diuresis control, requires dynamic monitoring of blood pressure due to the risk of its excessive decrease, especially in the case of receiving a large volume of urine in a short time. The frequency of blood pressure measurement is determined by the initial blood pressure figures, pharmacological history and depends on the doctor's experience. A pharmacological test with β 2 -adrenomimetics in a patient with bronchial asthma can solve diagnostic problems, so the detection of hyperreactivity or irreversibility of obstruction affects the tactics of further pharmacotherapy - the addition of anti-inflammatory drugs or an increase in their dose.

The results of the pharmacological test help determine an effective and safe starting dose of the drug. The choice of control methods when conducting a pharmacological test should correspond

meet the objectives of the study, and the chosen methods - have the necessary resolution.

The comparative value of methods of objective control of pharmacotherapy depends on the specificity of the changes detected with their help for the effect of a given drug. Methods that make it possible to quantitatively characterize controlled changes have advantages, but only if they are no less specific.

10.7. MEDICINAL DOSE TITING

The choice of the drug dosage regimen can be standard, recommended by the creators of the drug. The dosage regimen of the drug may be influenced by the characteristics of the course of the disease. The dosage regimen can be adjusted according to the results of the pharmacological test, taking into account the individual response to the drug.

During treatment, the dose of the drug can be changed depending on the dynamics of the pathological process under the influence of pharmacotherapy. In recent years, the technology of titration or dose titration has been used - a slow, stepwise increase in the individual tolerated dose of the drug with strict objective control of predicted adverse reactions and direct pharmacodynamic effects (for example, selection of the dose of a β-blocker in CHF).

10.8. EFFICIENCY AND SAFETY CONTROL

WHEN CARRYING OUT PHARMACOTHERAPY

When carrying out long-term or continuous pharmacotherapy, the treatment is monitored according to an individual program designed to provide an effective and safe individualized pharmacotherapy.

To solve the problems of course pharmacotherapy, you need to know:

Criteria characterizing the stabilization of the patient's condition;

Dynamics of parameters reflecting the effectiveness and safety of the selected drug;

The period of time after which the initial changes in the controlled parameters should be observed;

The expected time of the onset of the maximum therapeutic effect;

The time of the onset of stabilization of clinical parameters;

Criteria for dose reduction or drug withdrawal due to the clinical effect obtained;

Indicators, a change in which may indicate the slipping away of the effect of the therapy;

Time and risk factors for the possible manifestation of adverse drug reactions;

The dynamics of parameters reflecting the occurrence of adverse drug reactions.

The answers to the questions posed constitute a program for monitoring the patient's pharmacotherapy. The program should include mandatory and optional research methods, determine their frequency, sequence and application algorithm. In some cases, a contraindication to the use of drugs is the lack of a necessary control method, for example, the use of antiarrhythmic drugs in the absence of ECG monitoring methods for complex rhythm disturbances.

We have to abandon the use of drugs that have a high risk of developing severe adverse drug reactions in patients who violate the regimen of taking drugs, suffer from memory impairment if it is impossible to ensure control of drug intake, if the doctor is not sure that the patient will follow the recommendations when using

When carrying out drug therapy for patients with chronic diseases, even if the patient receives only preventive therapy and is in remission, examination is carried out at least once every 3 months.

Particular attention should be paid to the dosing regimen when conducting long-term drug therapy with a small therapeutic range. In such cases, only drug monitoring helps to avoid severe adverse reactions.

With the great importance of paraclinical examination methods in the control of the ongoing pharmacotherapy and the need for their use, medical supervision should be primary.

The dynamics of the patient's subjective sensations (for example, pain, itching, thirst, sleep quality, a feeling of shortness of breath or suffocation, increased exercise tolerance) and the dynamics of objective signs of the disease can be chosen as clinical criteria. Objective criteria are very important, and their search is desirable in all cases, including the use of drugs, the effect of which is assessed mainly subjectively (for example, analgesics, antidepressants). It should be noted that the disappearance of any symptom of the disease may be accompanied by an expansion of the range

functional capabilities of the patient. This can be detected using certain objective tests (for example, an increase in the range of motion of the affected joint after taking an analgesic, changes in behavior and intellectual disability after using antidepressants).

The criteria for the effectiveness or undesirable action of a drug are changes in the patient's condition that are caused by the use of this drug. For example, a convincing indicator of the anticoagulant effect of heparin is the prolongation of the blood coagulation time. You cannot ignore the patient's opinion about the action of drugs. In some syndromes, it can be the leading one in assessing the effectiveness of the drug (for example, pain syndrome and its relief).

10.9. THE PATIENT'S ADHERENCE TO TREATMENT

Patient's adherence to treatment, or compliance (from the English word compliance),involves the patient's conscious participation in the selection of drugs and self-monitoring of pharmacotherapy. The main factors that adversely affect the patient's adherence to treatment include:

Lack of trust or lack of trust in the doctor;

Lack of understanding by patients of the true state of their health and the need for drug therapy;

Failure to comply with the instructions for the use of drugs received from the doctor, due to the low level of education of the patient, decreased memory, cognitive functions in the elderly and with mental disorders;

Complex scheme for taking drugs;

A large number of simultaneously prescribed drugs, including when they are prescribed by doctors of different specialties;

Improvement of well-being (the patient may prematurely stop treatment or change the regimen of drug use);

Development of unwanted drug reactions;

Distorted, negative information about drugs received at the pharmacy, from relatives or friends;

The cost of the medicine and the patient's financial situation. Unsatisfactory patient adherence to drug prescription

(for example, unauthorized withdrawal of drugs) can lead to undesirable drug reactions, up to severe, life-threatening complications. It is dangerous and unauthorized change of the dosage regimen

Drugs, as well as self-inclusion in the treatment regimen of other drugs.

Patient adherence can be increased by clarifying the following points:

Clearly indicate the name of the drug;

It is easy to explain the goals of taking drugs;

Indicate the estimated time of the expected effect;

Give instructions in case of missing drug intake;

Indicate the duration of treatment;

Provide explanations on how to identify adverse drug reactions;

Explain how drugs affect the patient's life (for example, driving a car);

Indicate the possible interaction of drugs with alcohol, food, smoking.

Elderly people and patients with impaired memory should be given written instructions for the entire pharmacotherapy regimen. The same category of patients can be recommended to place drugs in advance in containers (jars, boxes, paper or plastic bags) indicating the time of admission.

A promising direction for increasing patients' adherence to treatment is the development of educational programs for patients (creation of schools for patients with bronchial asthma, diabetes, peptic ulcer and other diseases). It is necessary to train patients in the framework of educational programs in self-control methods, including using individual control devices (peak flow meters, glucometers, blood pressure, heart rate control devices, etc.), self-correction of treatment and timely access to a doctor. The analysis of the patient's treatment control diary contributes to the improvement of the quality of individualized therapy.

10.10. FEATURES OF PHARMACOTHERAPY OF URGENT CONDITIONS

The doctor experiences great difficulties in carrying out pharmacotherapy in urgent situations when the patient depletes the functional systems and may experience paradoxical reactions to the injected drugs, which increases the risks of NDL development. In such a situation, pharmacotherapy requires a doctor to have deep medical knowledge, promptness in the selection and use of adequate doses of drugs.

It is extremely difficult to predict the individual choice and nature of drug dosage in such a situation, since it depends on specific clinical situations and the dynamics of the main functional indications. At the same time, certain requirements are imposed on the pharmacokinetic properties of drugs and on the form of release of the necessary drugs. The selected drug should have pharmacokinetic properties and dosage form that allow good control of pharmacological effects. It should be a water-soluble preparation with a short half-life in ampoule form.

For example, the goal of pharmacotherapy for acute pulmonary edema is to urgently eliminate left ventricular overload. At the same time, taking into account the severity of the patient's condition, the pathophysiology of the development of the disease, the state of central and peripheral hemodynamics, drugs with different pharmacodynamic effects can be selected - drugs with a positive inotropic effect or vasodilators that relieve preload (nitrates, enalapril), antiarrhythmic drugs or diuretics, reducing the volume of circulating blood, as well as combinations of these drugs.

10.11. FEATURES OF LONG-TERM PHARMACOTHERAPY

When carrying out long-term pharmacotherapy, constant attention of the doctor is necessary, since a change in the patient's condition can be associated both with the nature of the course of the disease and with the pharmacotherapy being carried out.

Let's consider several situations that arose during its implementation.

An increase in the concentration of the drug or its active metabolites above the therapeutic level due to the individual characteristics of the drug kinetics in the patient. This can lead to the development of an excessive direct pharmacological effect and increases the risks of developing adverse drug reactions.

Restoration of disorders in the regulation of various body functions, enhancement of compensatory reactions, can enhance the pharmacological effect at the same drug concentration. In both cases, it is necessary to reduce the dose of drugs, and in some cases, drugs should be canceled.

A more complex situation is noted with a decrease in the clinical efficacy of the drug, which is observed not only at low, but also at high concentrations of drugs, when the sensitivity and number of receptors decreases, the regulatory system at the cellular level is disturbed (β-stimulants in bronchial asthma, cardiac

glycosides, etc.). Differentiating the cause of the escape of the effect in most cases is possible only by determining the equilibrium concentration of drugs in the blood plasma. If the concentration of the drug is reduced, which may be due to a change in the patient's kinetic parameters, the dose is increased. If the concentration of drugs in blood plasma remains at a therapeutic level, then the drug used must be replaced with another, with a different mechanism of action.

With some diseases, as well as congenital and acquired pathological conditions, there is a need for supportive pharmacotherapy for a long time, sometimes for life. This is the case in the following cases:

When drugs are used as a means of replacement therapy (for example, insulin in type 1 diabetes mellitus);

When forming a variant of the course of the disease with drug dependence and the threat of death due to drug withdrawal (for example, glucocorticoids in hormone-dependent bronchial asthma);

When correcting persistent functional disorders that significantly affect the patient's adaptation to the environment and the prognosis of the disease (for example, lifelong use of ACE inhibitors, β-blockers in CHF patients).

At the 4th stage, the pharmacotherapy is corrected if its effectiveness is insufficient or when new complications of the disease appear.

In this case, it is necessary to change the approach to the choice of drugs or decide whether to use a combination of drugs. For a number of drugs, it is necessary to be able to predict and detect a decrease in the effect as they are used as a result of tachyphylaxis, acceleration of metabolism due to the induction of liver enzymes, the formation of antibodies to the drug, and for other reasons. During the observation process, various solutions are possible:

Short-term interruption of the drug (nitrates in patients with exertional angina);

Increasing the dose of the drug (clonidine);

Replacing the drug with a new drug;

Transition to combination therapy.

The need to correct pharmacotherapy may arise when the clinical condition is stabilized. In this case, it is necessary to either cancel the drug or switch to maintenance therapy. It should be borne in mind that some drugs require a gradual dose reduction, these include: amphetamine, antidepressants, protivo-

road drugs, many drugs used for diseases of the cardiovascular system (clonidine, methyldopa, β-blockers, blockers of slow calcium channels), systemic glucocorticoids with their long-term use, opiates, etc.

10.12. ERRORS IN EVALUATING ACTION

MEDICINAL PRODUCT

Errors in assessing the effect of a drug are most often associated with insufficient consideration of the fact that the identification of changes expected from its action does not in itself prove a causal relationship of changes with the pharmacological effect of a given drug. The dynamics of the observed trait can also be caused by such reasons as:

Psychotherapeutic effect similar to placebo;

The adjacent effect of another drug simultaneously applied (for example, the disappearance of ventricular extrasystoles under the action of an antianginal drug, and not an antiarrhythmic drug used simultaneously);

Recovery of impaired function not related to treatment - regression of the pathological process, remission of the disease, cessation of exposure to pathogenic factors and the emergence of conditions for the activation of compensatory mechanisms.

A correct assessment of the relationship between signs of improvement in the patient's condition with the action of drugs allows you to timely cancel unnecessary drugs with sufficient contiguity of the effect or replace them with more effective ones.

10.13. CANCELLATION OF DRUGS

Justification of drug withdrawal and cancellation is the final stage of pharmacotherapy. Continuation of pharmacotherapy after the cure of the disease is contraindicated. In the process of complex pharmacotherapy, the need to cancel a certain drug or their combination is justified by the achievement of the goal of pharmacotherapy, which is usually associated either with the completion of the pathological process (for agents of etiotropic and pathogenetic treatment), or with the restoration or compensation of any function, the violation of which determined the indications for the appointment of this drug. In addition, the rationale for canceling drugs in the course of therapy can be:

Reduction or disappearance of the therapeutic effect due to the peculiarities of the pharmacological action of the drug

or the formation of irreversible changes in the target organs during the course of the disease;

The predominance at any stage of contraindications over indications for drugs according to the dynamics of the pathological process or due to the increase in time of the risk of dangerous consequences of the use of the drug, a special case of such a justification for cancellation is the completion of the course for drugs with a regulated course dose or duration of use;

Manifestation of toxic or side effects of drugs, excluding the possibility of replacing the drug (digitalis intoxication when using cardiac glycosides).

Cancellation of drugs is contraindicated if it is the only means of maintaining vital functions - respiration, blood circulation, metabolism. A contraindication to discontinuation of the drug may also be the supposed decompensation of functions that ensure adaptation of the patient to the environment due to its cancellation.

If there are indications for cancellation and there are no contraindications to it, the doctor determines the required rate of cancellation, taking into account the changes in the body caused by the drug. This applies to the greatest extent to drugs acting at the level of the regulatory system with feedback structures, primarily to hormones and mediatory agents. For example, the sudden withdrawal of clonidine in patients with arterial hypertension can cause severe hypertensive crises.

Possible options for canceling drugs are:

Termination of drug administration, which is possible for the vast majority of drugs in the case of short-term use;

Cancellation by gradually reducing the daily dose in the time necessary for the regression of functional changes (for example, increased sensitivity of adrenergic receptors due to the use of sympatholytics) or to restore the suppressed drug function;

Cancellation under the guise of another drug that prevents the development of undesirable consequences of withdrawal (for example, withdrawal of clonidine with the addition of β-blockers or other antihypertensive drugs).

Each of the listed options is chosen taking into account the prognosis of the withdrawal syndrome based on specific data on the pharmacodynamics of the drug and the functional state of the systems involved in the manifestations of the pharmacological effect.

10.14. COMBINED APPLICATION

MEDICINAL PRODUCTS

The amount of required pharmacotherapy determines the indications for complex pharmacotherapy, i.e. to the use of drugs for various purposes.

An indication for complex pharmacotherapy may be the presence of two or more different pathological processes in a patient due to complications or concomitant diseases, each of which requires drug treatment, or features of the course of the disease that require the simultaneous conduct of both etiotropic and pathogenetic or symptomatic pharmacotherapy.

The goals of drug combinations are to enhance the therapeutic effect (with insufficient effectiveness of one drug), reduce the dose of a toxic or drug that has undesirable effects, and neutralize the undesirable effect of the main drug.

The choice of drug combination is one of the most difficult elements of pharmacotherapy. The combined use of drugs is carried out in accordance with the general principles of pharmacotherapy, using the same technologies for the use of drugs that were discussed above. At present, competent combined pharmacotherapy is impossible without taking into account the achievements of clinical pharmacology in the study of the mechanisms of drug interaction.

Individualized combination therapy is impossible without taking into account the peculiarities of the pathogenesis of the disease and its manifestations in a given patient, assessing the degree of functional disorders, the presence of concomitant diseases, the nature of the course of the disease, the urgency of the situation, the patient's personality characteristics, as well as the compatibility of drugs if it is necessary to combine them and other data as about drugs , and about the patient.