The main goal of pharmacotherapy. Pharmacotherapy

It is always necessary to evaluate the risk and benefit ratio, since the purpose of any drug is associated with a certain risk.

The response to pharmacotherapy depends on both the characteristics of a particular patient and its behavior, habits (use of certain food and food additives, following the prescribed drug dosing regime), the presence of renal or liver failure, other concomitant diseases, reception other drugs. Errors when prescribing drugs (the choice of an inappropriate drug, the erroneous reading of the recipe, the improper reception of the drug) also affect the effectiveness of treatment.

Adherence to the appointed pharmacotherapy

Commitment (compliance) is a measure of how strictly the patient follows the prescribed treatment plan. In the case of drug therapy, compliance with the prescribed mode involves the timely preparation of the drug and its reception in accurately according to the prescribed dose, the multiplication of the reception and the duration of treatment. Patients should be recalled that in case of discontinuation of either deviation from the prescribed diagram of the drug, it is necessary to inform the doctor that in practice rarely occurs.

Only approximately half of patients take medicines according to the appointments made by the doctor. The most frequent causes of the absence of pharmacotherapy commitment are:

• the need for frequent reception;
• denial of the presence of the disease;
• misunderstanding of drug therapy benefits;
• cost of treatment.

There are other reasons. Children to a lesser extent tend to adhere to the appointed treatment regimen. The lowest compliance is observed in chronic diseases requiring comprehensive long-term treatment. Parents may not fully understand the instructions on the use of drugs and after 15 minutes forget half of the information received from the doctor.

Elderly patients keep therapy regime to the same extent as other adult patients. However, the factors that reduce compliance (for example, financial difficulties, the use of several drugs or drugs requiring multiple reception per day) are more common among elderly patients. Cognitive disorders can lower compliance with even greater degree. Sometimes the doctor prescribing the drug is forced to show a creative approach when choosing a drug, assigning the easiest to use from existing analogues. For example, in patients with arterial hypertensionClonidine can be appointed in the form of a transdermal therapeutic system in the form of a transdermal therapeutic system, which should be replaced by a weekly medical sister or family members.

The most obvious result of non-compliance with the prescribed mode of therapy is the impossibility of facilitating the patient's condition or to achieve its cure. It is believed that this circumstance annually leads to 125,000 fatal outcomes among patients suffering from cardiovascular diseases. Compliance with patients prescribed therapy regime could prevent up to 23% of the premises in the nursing homes, up to 10% of hospitalizations, many visits to doctors, diagnostic research and many types of unnecessary treatment in this case. In some cases, reduced compliance may lead to an increase in the severity of the disease. For example, the passage of reception or the early cancellation of antibacterial or antiviral therapy contributes to the growth of the resistance of pathogens.

Pharmacists and pharmacists in pharmacies, medical sisters can help identify and resolve problems associated with non-compliance with prescriptions. For example, a pharmacy officer may noted that the patient does not come to re-obtain the prescribed drug, or does it prematurely. Discussing prescribed prescribed prescribed together with the patient, a pharmacy officer or nurse Can reveal and help eliminate misunderstanding or fears of the patient. The doctor can change the complex or frequent patient for the treatment of the drug, or replace the latter to a safe, efficient, but cheaper preparation.

Errors when appointing medicines

Errors associated with the purpose of drugs lead to an increase in the frequency of complications of pharmacotherapy.

Their main reasons:

• Improper selection of drugs, destination it in an inadequate dose, incorrect dosing mode and / or the duration of the course of therapy.
• The erroneous reading of the recipe by the pharmacy officer, as a result of which the wrong drug is released or its dosage.
• The erroneous reading of the packaging by an employee of the pharmacy, as a result of which the wrong drug is released or its dosage.
• Invalid instructions to the patient.
• Incorrect administration of the drug with a medical worker or patient.
• Improper storage of the drug by a pharmacy or patient, which leads to a decrease in its activity.
• The use of drugs with an expired shelf life, which leads to a decrease in their activity.
• Wrong medication intake by the patient.

Errors in the purpose of medicinal products are very frequent, especially in certain categories of patients. The risk group includes the faces of the elderly, women of childbearing age and children. Medicinal interactions are especially common in patients receiving several drugs. To reduce risk, you need to know all the drugs taken by the patient (including other doctors assigned and released without a recipe) and maintain their list are relevant. Patients need to be convinced of the need to compile full list Accepted drugs to provide his attending physician or other health care if necessary. The recipe must be written as clear as possible.

The names of some drugs are similar to what can cause confusion if they are written unintelligible. Avoid mistakes helps to decrypt some traditional designations that may be incorrectly read. For example, "1 p / d" is easily confused with "4 p / d", therefore it is preferable to write "once a day." The use of recipes printed on the printer helps to avoid problems associated with rally handwriting or incorrect abbreviations.

Errors when prescribing medicines are also possible in medical institutions. In particular, the drug can not be issued to the patient, not at that time, or the wrong method of its introduction is wrong. Some drugs should be administered intravenously slowly; Some - you can not enter in parallel. When identifying such errors, it is necessary to immediately inform the doctor and get advice from the provision. Electronic vacation systems of drugs reduce the likelihood of such errors.

Preparations should be stored in such a way as to ensure the preservation of their activity. Pharmacies causing drugs by mail should also comply with the necessary transport rules. Often, drugs are incorrectly stored by patients, and in this case the likelihood is increasing that they will lose their effectiveness long before the expiration date. The packaging should be clearly indicated whether the drug should be stored in the refrigerator or in a cool place that protects from the effects of high temperatures or sun rays, or by observing special storage conditions. On the other hand, unnecessary precautions reduce the likelihood of compliance with the prescribed therapy regime and lead to unnecessary patient time consumption. For example, insulin in unopened packaging should be stored in the refrigerator; However, the outdoor bottle can be stored for a long time Outside the refrigerator, in a place excluding the effect of overly high temperatures or direct sunlight.

The use of drugs with an expired expiration date is quite common. Such preparations usually lose activity and in some cases (for example, acetylsalicylic acid or tetracycline) are dangerous.

Most often mistakes occur in the absence of information in patients on how to make the drug correctly. As a result, they may not erroneously accept the drug or the irregular dose of the drug. Therefore, patients should receive information about what dose of the drug should be taken and why this drug was appointed. It is desirable that this information be saved in a patient in writing. It should also be recommended to consult a pharmacy officer about the use of the drug. Packaging must be comfortable, but safe. In the absence of the likelihood of access of children to drugs and the presence of difficulties in a patient with the discovery of a container with a drug, a simple packaging should be used without the mechanisms of protection from the opening of children.

Medicinal interactions

Medicinal interaction is a change in the effects of the drug, due to the recent or simultaneous taking of two or more medicines (intersectoral interaction) or by receiving the drug in conjunction with food.

Medicinal interaction can lead to strengthening or weakening the effect of one or several combination drugs. Clinically significant interactions are often predictable and usually undesirable, because May lead to the manifestation of side effects, or the absence of a therapeutic action. Less often clinicians can use predictable interstices interactions to achieve the desired therapeutic effect. For example, the simultaneous purpose of the Lopinavir and the ritonavir patient with HIV leads to a slowdown in the metabolism of the Lopinavir and the increase in its plasma concentration, which increases the effectiveness of therapy.

With simultaneous reception of two drugs with similar properties, the summation of their effects is possible. For example, when taking a patient of one benzodiazepine as a tranquilizer and the other - as a sleeping pills for the night, their cumulative effect can lead to the manifestations of toxicity.

Drug interactions are divided:

• on pharmacodynamic,
• pharmacokinetic.

In pharmacodynamic interaction, one drug changes the sensitivity or reaction of the body to another, possessing similar (agonistic) or opposite (antagonistic) effect. These effects are usually implemented at the receptor level, but may occur as a result of influence on intracellular systems.

With pharmacokinetic interaction, one of the combination preparations usually changes the absorption, distribution, binding to proteins, metabolism or elimination of the other. Accordingly, the number and duration of the impact of the first preparation on the receptor. Pharmacokinetic interaction changes the severity and duration of the effect, but not its type. Often, it can be predicted, based on the characteristics of individual preparations, or to identify in the process of monitoring their concentration or clinical symptoms.

Minimization of interacial interactions. The attending physician should know about all medicines that the patient takes, incl. Appointed by other specialists released without a recipe, as well as food additives. It is desirable to interview the patient about the nature of the nutrition and drinking alcohol. A minimal amount of the drug should be prescribed in a minimum effective dose for the shortest period of time. It is necessary to determine the effects (desired and side) of all taken preparations, since they typically include the spectrum of potential drug interactions. In order to avoid manifestations of toxicity due to unpredictable drug interactions, preparations should be used with a wider therapeutic range.

Patients need to be observed for the development of unwanted reactions, especially after the changes in the treatment regimen; Some types of interactions (for example, as a result of the induction of the enzyme) may manifest a week or later. Medicinal interaction must be considered as a possible cause of any unforeseen complications. In the development of an unexpected clinical reaction, the doctor may require the definition of the concentration of individual accepted blood serum drugs. Based on this information, as well as obtaining relevant information in the literature or at the expert - clinical pharmacology, it is possible to proceed a dose until the desired effect is achieved. If the dose correction turns out to be ineffective, the drug must be replaced by another, not interacting with those that receive the patient.

Pharmacogenetic

Pharmacogenetics studies the differences in a pharmacological response depending on the genetic structure of the body.

The activity of enzymes, metabolizing drugs, often varies in large limits in healthy people. As a result, the elimination rate of one or another drug may differ ten times. The causes of most of these differences are genetic factors and aging.

Genetically deterministic changes in the metabolism of the drug (for example, due to various activity of enzymes carrying out its acetylation, hydrolysis, oxidation or other transformations) may have clinical consequences. For example, patients rapidly metabolizing some drugs may need to assign higher doses or more frequent multiplicity of their admission to achieve the therapeutic concentration of the drug in the blood. At the same time, patients slowly metabolizing certain drugs, in order to avoid intoxication, it may be necessary to prescribe a drug in smaller doses with a smaller reception multiplicity, in particular, it concerns drugs with low latitude of therapeutic action. For example, in patients with inflammatory diseases The intestines that are required to assign an azatiotrospin is carried out genotyping of thiopurinmethyltransferase (TMT) to determine the optimal starting dose of the drug. Most genetic differences cannot be predicted before the drug is prescribed, however, for an increasing number of drugs (for example, carbamazepine, clopidogrel, warfarin) variability, efficiency and risk of toxicity can be associated with certain genetic differences. In addition, the interaction of environmental factors and the patient's body is possible, which leads to a change in the response to drug therapy.

Placebo

Placebo - inactive broadcasting or interference, often used in controlled studies for comparison with potentially active drugs.

The term placebo (lat. "I like") originally called inactive, harmless substances that were given to patients in order to improve their well-being under the action of suggestion. Later, fictitious interventions (for example, false electrostimulation, simulated surgical procedures began to be calculated. The term is sometimes used to designate active drugs appointed exclusively as a placebo in diseases, for the treatment of which they are actually ineffective (for example, an antibiotic for patients with viral infection). The manifestations of the placebo effect are more often subjective (for example, headache, nausea), rather than an objective nature (the healing rate of the wounds, the degree of infection of the burns).

Effects. Although placebo is physiologically inactive, they can have a real effect - positive or negative. These effects are usually associated with the expectation that the drug will act; Waiting for unwanted reactions is sometimes called a nocebo effect. The placebo effect usually occurs with subjective reactions (for example, pain, nausea), and not objective (for example, the healing rate of ulcers, the level of infection of burn wounds).

The rate of placebo response depends on many factors, such as:

• the manifestation of confidence in the positive effect by the doctor ("This drug will help you feel much better" against "there is a chance that he will help you");
• waiting for the patient (the effect is greater if the patient is confident that he receives an active substance than when he knows that it may be receiving a placebo);
• placebo type (substance for intravenous administration has a large effect compared to the received orally).

The placebo effect is not observed in all patients, moreover, it is impossible to predict in advance who he will manifest itself. The relationship between the features of the personality and the reaction to the placebo was repeatedly discussed, but in reality is not fully established. Nevertheless, patients who feel strong dependence on a doctor or seeking to please him, with a greater probability will be observed positive effects; Expressive individuals will more often declare the appearance of effects, both positive and negative.

Use in clinical studies. In many clinical studies, the effect of active treatment is compared with placebo. The alleged placebo effect should be deducted from the general observed effect, to determine the true therapeutic effect. In other words, it is necessary to evaluate clinical and statistically significant differences. In some research, placebo facilitates the symptoms of the disease in a significant proportion of patients, which makes it difficult to determine the effect of active treatment.

Use in clinical practice. In rare cases, placebo can be appointed when the doctor decides that the patient's disease has a slight course, and does not require the appointment of active drugs or when effective treatment is absent in principle (for example, in the case of non-specific disabilities, fatigue). It is often justified by the fact that it satisfies the patient's desire to receive treatment without exposing it to risk adverse Reactions And in some cases, facilitating well-being (due to the placebo effect or spontaneous improvement).

Ethical aspects. In clinical studies, the subject of ethical discussion is the question of the admissibility of the placebo use as such. When there is effective treatment (for example, opioid analgesics with severe pain), it is usually considered to be unethical to detect the participants in the treatment of treatment by appointing placebo. In such cases, patient control groups receive standard active treatment. Since the research participants are aware of pre-aware that there is a possibility of receiving placebo, there is no concern about the intentional deception.

At the same time, when the patient is prescribed placebo in real clinical practice, he does not talk about receiving inactive treatment. In this case, the efficiency of the patient's injury becomes controversial. Some clinicians consider this approach initially unethical and, if it becomes known that harm the relationship between the doctor and the patient. Others argue that it is much more unethical not to prescribe any treatment to the patient, thereby depriving it to feel better. Purpose patient pharmacologically active preparation Exceptionally, as a placebo, it is also possible to consider as contrary to the principles of bioethics, since in this case the patient is at the possible risk of real side effects (as opposed to a noce-effect).

Research of new medicines

Potential medicinal substances can be found through full-scale screening of hundreds and thousands of molecules for biological activity. In other cases, the knowledge of specific molecular aspects of the pathogenesis of a disease allows the use of a rational approach to creating new drugs by computer simulation, or modifying existing pharmacologically active molecules.

During early preclinical studies, potentially active compounds are studied on animals to assess the desired action and toxicity. Substances that showed their effectiveness and security become candidates for further study in humans. In the US, a protocol comprising a description clinical researchIt should be approved by the Expert Council of the relevant institution and the United States Food and Medicinal Control Office (FDA), which then issue permission to study a new drug. From that moment, the period of action of a patent for the drug, usually gives the owner exclusive rights for the next 20 years; However, the drug can not be released to the market without approval of the FDA.

During the clinical study phase 1, the safety and toxicity of the drug in humans is estimated. For this, various doses of the substance studied are taken by a small number (usually from 20 to 80) healthy volunteers (usually young men) to determine the dose at which the first signs of toxicity arise.

The aim of phase 2 is the confirmation of the activity of the drug with a specific pathology. The preparation studied is prescribed to a group of up to 100 patients to treat or prevent this pathology. An additional task of this phase is to determine the optimal dosing mode.

In phase 3 studies, the effect of the drug is estimated on more numerous (from 100 to several thousand people) and heterogeneous groups of patients to confirm the possibility of the clinical use of the studied drug. During this phase, a comparison is also compared with existing standard patterns of therapy and / or placebo. Practitioners and many medical institutions can be involved in the study. The main purpose of this phase is to confirm the effectiveness of the drug and its possible effects (both positive and negative), which may not be detected in the studies of the 1st and 2nd phases.

When sufficient data will be collected for registration of the drug, the materials are submitted to a controlling organization that gives permission to issue it to the market. Since the early stages of drug development, about 10 years have often passed to registration.

Phase 4 studies are carried out after the drug receives registration and comes on sale. Such research is usually continuous and involved in large populations of patients. Often, special subgroups of patients are included in such studies (for example, pregnant, children, elderly patients). Studies 4th near the phase also suggest regular reports on undesirable phenomena developed when using the drug. Some drugs approved by the FDA after Phase 3 were recorded from sale after identifying 4 new major side effects in the phase.

Stenzardia is the most frequent manifestation of coronary heart disease (IBS) in our country. According to statistics for 2003, angina revealed in 2,720,000 inhabitants of Ukraine, which is 37% of all cases of diagnosed IRS (7,772,619) and 40% of all cases of newly identified IBS (258 337).

N.N. Bezuless, Ph.D., Department of Faculty Therapy No. 1 National Medical University. A.A. Bogomolets, Kiev

How important is the problem of angina?

This corresponds to the data obtained in the UK, where, when analyzing 295,584 cases, for the first time identified by IHD found that the stress angina is the most frequent first manifestation of IBS - 46%, it is 27%, a sudden death - 14% and unstable angina - 13% (SUTCLIFFE S. et al., 2003). At the same time, the average frequency of angina a year is 213 per 100,000 population over 30 years (Elveback L. et al., 1986).

The prevalence of angina in Ukraine compared with 1999 increased by 64% and is approximately 2 times higher (5, 7% of the population) than in the United States (3.8% of the population). At the same time, the mortality rate from the IBS in the structure of all causes of death in Ukraine is also 2 times higher than the Middle Equipment and statistical data of the US statistics (41%, 22% and 20%, respectively; British Heart Foundation. European Cardiovascular Disease Statistics 2000).

The effects of angina disease. The occurrence of angina region leads not only to the deterioration of the quality of life (reducing the tolerance of physical and psycho-emotional loads), but also 3 times the risk of occurrence unstable angina And the development of them, and therefore leads to an increase in the risk of death. During the first year after the occurrence of angina phase, 10% of patients are developing or they die, another 20% require revascularization (Gandhi M. et al., 1995). According to various sources, angina region precedes from 20 to 50% of all cases to them (Rouleau J., 1996; Hurst W., 2002).

Stenzardia is not only direct costs of outpatient and stationary examination, for payment of treatment, but also indirect costs associated in the temporary and rescue disability of the patient who are a heavy burden for society, health care, patients and their families. For example, in the UK in 2000, 2,35 million visits to the doctor, 16 million issued recipes, 149,000 hospitalities, 117,000 angiography, 21,400 AKS and 17,700, were 2.35 million patients with angina region. EUR. Heart J., 2002, 4, 720).

If angina phase 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 (or death) in persons with high risk. The CHA is the cause of death of approximately every second inheritant of our country.

Problems of pharmacological treatment of angina. The following traditional and interrelated challenges of angina: low-quality diagnostics and inadequate treatment can be distinguished. Non-quality diagnosis can lead to steadfast label and as a result of this to the appointment of unnecessary treatment, an increase in the level of neurotic, unnecessary additional examination and hospitalization, as well as to the absence of a treatment effect.

Specific problems of pharmacological treatment of angina region are as follows.

1. Treatment of atypical pain syndrome as a classic angina region (the diagnosis is not verified).
2. Insufficient treatment:
   • low doses of antichangal drugs;
   • lack of control over the heart rate in the treatment of β-blockers.
3. Polypragmasia (many unnecessary drugs).
4. Risk factors are not revealed and not corrected.

The purpose of the treatment of stable angina. Getting Started with patients with stable angina, it is necessary to clearly represent that there are only two goals of treating patients with such a diagnosis. The first is the prevention of them and death, which means the extension of life. The second is a decrease in the symptoms of angina, which leads to improved quality of life. Naturally, treatment aimed at extending life is a priority. In the event that there are two different methods of treatment (preparation), equally effective in the elimination of angina symptoms, preference has the type of treatment that extends life.

Improving the quality of life and forecasting of the disease suggests, on the one hand, the exact diagnosis of stable angina, and on the other - the determination of the degree of risk of developing complications. This depends on the choice of proper treatment, as it is different depending on the goal.

Prerequisite effective treatment It is also a good knowledge of the patient of the essence of his illness and understanding the meaning of treatment. For most patients, the purpose of treatment should be a complete or almost complete elimination of angular pain and return to normal life and functional abilities corresponding to the I functional class of angina. 82% of patients with stable stress angina limit everyday loads 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 concomitant diseases, a decrease in symptoms may be sufficient, which will ensure only limited load.

Sometimes it is quite difficult to assess such a subjective indicator as the quality of life and often the inconsistency between the opinion of the doctor and the patient arises. The doctor may assume that the designated treatment controls the attacks of angina, while the patient is confident in the opposite. In the study conducted in the UK, in which 5,125 patients with angina patients took part, half of the patients noted two or more attacks of angina per week, however, 62% of patients described their health status as "unsatisfactory" or "bad" (Pepine CJ et al . Characteristics of A CONTEMPORARY POPULATION WITH ANGINA Pectioris // American Journal of Cardiology, 1994, Vol. 74. 226-231).

What recommendations for the treatment of stable angina is currently? We must use recommendations for the treatment of stable angina European society Cardiologists (ESC, 1997), their newer option - recommendations of the American Heart Association (Ass / Ana, 2002), as well as the most new option - recommendations of the American College of Doctors (ASS, 2004). In the spring of 2005, the emergence of new recommendations for the treatment of stable angina of the European Society of Cardiologists are announced, as it is clear that the current ESC recommendations are already essential.

Medicase treatment of angina, aimed at preventing them and death

Antitrombocytic drugs. The growing importance of antithrombotic drugs led to the publication of separately developed recommendations of the European Society of Cardiologists for their use (Patrono C. et al., 2004). The drugs of this class should be appointed routine and for a long time to all patients with a diagnosis of CHD, even if there are no symptoms of angina. According to these recommendations, the selection drugs are aspirin at a dose of 75-150 mg per day and clopidogrel 75 mg per day.

The value of clopidogrel is growing - the only antithrombocytic drug is proved better than aspirin, in the prevention of them, stroke and vascular death. The combination of aspirin and clopidogrel leads to an even greater increase in the effectiveness of treatment. The need for this is in the case when the patient has already suffered any complication of atherotromability - acute coronary syndrome or stroke, as well as after coronary angioplasty. Dipyridamol should not be used to be more used with IHD both in the form of monotherapy and in combination, as it can provoke myocardium ischemia (Patrono C. et al., 2004).

β-blockers. Showing for long-term admission to all patients with IBS in the absence of contraindications, as the survival rate, the frequency of repeated and symptoms of ischemia is improved. Sugar diabetes is no longer a contraindication to the purpose of β-blockers - their effectiveness in these patients is even higher. In the recommendations of the European Society of Cardiologists, the β-blockers are recommended as initial treatment in the absence of contraindications, especially in patients who have undergone them, as the mortality rate (Swedberg K. et al., 2004) is reduced.

In the presence of bradycardia, sinus node dysfunction or AV blockade β-blockers can lead to the development of symptomatic bradycardia or more high degree blockades. In addition, β-natives are contraindicated to patients with bronchial asthma. In patients with obstructive diseases of the lungs, insulin-dependent diabetes and severe vascular pathology lower extremities Treatment should begin with very small doses.

The higher the heart rate in the patient alone, the higher the efficiency of β-blockers. The decrease in heart rate during treatment can reach 55 per minute, provided good tolerability and the absence of symptomatic hypotension. Preferences have preparations without internal sympathomimetic activity. The basic principle of the use of β-adrenoblockers is the appointment of them in doses, providing a distinct effect of the blockade of β-adrenoreceptors. To do this, it is necessary to achieve the decline in heart rate alone up to 55-60 per minute, which is not always achieved in real clinical practice and is accompanied by a pronounced effect.

Lipid lining drugs. Statins must be appointed to all patients with IBS. It remains an open question, what should be the target level of lowering LDL? To date, this level was less than 100 mg / dl.

However, in 2004, revolutionary changes in the field of hypolypidemic therapy occurred. Based on the results of recent studies of HPS and PROVE IT, in a specially published add-on to the generally accepted recommendations of the NCEP ATP III in the group of high-risk patients (diabetes mellitus, metabolic syndrome, smoking, who suffered acute coronary syndrome) recommended a new target level of lowering LDL levels less than 70 mg / For (Grundy S. et al., 2004).

Currently, all the statins available at our disposal have randomized studies with "solid endpoints" and can be used in patients with angina. Simvastatin, Handustyatin and Atorvastatin are the greatest evaluative base on the efficiency and safety of treatment.

ACE inhibitors. In published recently consensus of experts of the European Society of Cardiologists on the use of ACE inhibitors with CVD (2004), it is indicated that the use of this group of medicines is required when dysfunction of the left ventricle and / or heart failure. With IHD without heart failure and dysfunction of the left ventricle, the effectiveness in reducing mortality is proved only for tissue inhibitors of ACE Ramipril and Perindopril. Only for these drugs, theoretical prerequisites and experimental data have found their confirmation in large randomized controlled Studies of Nore and Europa. The research results are so convincing that it was on their foundation a new indication for the appointment of ACE inhibitors - secondary prophylaxis Cardiovascular diseases without heart failure or left ventricle dysfunction (ESC, 2004). And in October 2004, American College of Doctors (ASS) on the basis of these studies recommended the reception of ACE inhibitors to all patients with stable angina, asymptomatic suspected or installed IHD.

The degree of reducing the risk of death in patients with IHD depends on the number of applications used. The risk of death is the lowest while using drugs of all four mentioned classes. With such complex treatment The highest possible degree of reducing the risk of complications of IBS and death is achieved.

Medicase treatment of angina, aimed at eliminating symptoms. In the treatment of angina drugs, three classes of antichangative preparations are used: β-blockers, prolonged Ca antagonists and nitrates, prolonged and short action (to relocate the attack of angina). Preparations of all these classes have proven efficacy in reducing the frequency of angina, both under monotherapy and with combined treatment. The choice of the drug, however, remains a difficult task due to the fact that no class showed its convincing superiority over the other, while the patient's individual response may be different.

Preparations of each of these classes reduce the pre- and post-load on the heart and can improve coronary blood flow, which eliminates the imbalance between the delivery and the need of myocardium in oxygen. Although monotherapy can be effective in some cases, most patients need to eliminate symptomatics requires the use of two or more antichangative preparations.

Nitrates. Nitrates do not need special recommendations And well studied. According to the recommendations on the maintenance of patients with a stable angiard of the voltage of the American and European Society of Cardiologists (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 relate to class I preparations.

Although nitrates and do not reduce the frequency of complications and mortality in patients with IBS, they have high efficiency both in the relief of the attack of angina (nitroglycerin sublingual or in the form of a spray) and in its prevention. If, recently, they say a little and write 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 in various randomized and epidemiological studies varies from 40 to 60%. The frequency of long-term reception of nitrates in the EUROPA study (2003) in 12,218 patients was 42.8%, in the study of Euro Heart Survey ACS (2002) from 10,484 patients 64.8% regularly accepted nitrates after the myocardial infarction.

The main problems in the prophylactic use of nitrates during angina are: the choice of the drug, the development of tolerance and the occurrence of headaches. With long-term treatment of angina, mononitrates are usually used. These drugs are active metabolites of the isosorbide of dinitrate, but in contrast to it are significantly better absorbed when taken inward, do not be biotransformation in the liver and have 100% bioavailability, which ensures the predicted concentration of the isosorbide mononitrate in the blood plasma and predictable therapeutic effect, since no change is required Dosages in disruption of the liver function. Currently, the recommended doses are 40 mg and 60 mg, a dose increases to 240 mg for retardious forms of mononitates. To achieve the effect, it is extremely important to use nitrates in effective doses, for the retalial form of mononitrate clinically effective in one-time application is a dose of 40 mg per day. Mononitrates in one-time application are more effective, provide a sufficient faulting period to prevent the occurrence of tolerance and the development of headaches (Sonda, 1995) is more reliably.

As far as it is important, the last study of Compass (2004) shows, in which the treatment with mononitrium at a dose of 60 mg per day was significantly more efficiently and was better transferred to patients than the use of nitrates 2 times a day. Conclusion with these data appointment of nitrates 3 times a day seems to be dubious.

Other drugs of this class do not apply to practical medicine Due to complete inefficiency (preparations of depot-nitroglycerin) or due to low efficiency (isosorbide dinitrate). The constant reception of transdermal drugs is limited due to the development of tolerance towards their hemodynamic and anti-inanimal effect.

Antagonists sa. There is a decrease in the value of this class of antianginal preparations. Initially, alertness in relation to them in the treatment of CHD was associated with the use of short-acting drugs in the form of monotherapy, as they increase the frequency of coronary complications and mortality.

However, despite the use of prolonged forms, a large number of studies and metaanalyzes, a position against Ca antagonists remains unchanged - these are the preparations of the second or third plan in the treatment of patients with angina, which are not reacting to the treatment with β-blockers and nitrates, the third or fourth plan - in the treatment AG, which are not reacting 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 proven the fact that prolonged dihydropyridines are also safe, as well as placebo, there is no data that would allow to assert how efficient placebo in reducing the frequency of complications and death, since nothing add to the treatment of patients with stable Stenicardium already receiving standard therapy with β-blockers, aspirin, nitrates and statins (Action, 2004).

Therefore, at present, the place of Nedigidropyridine antagonists of the CA in the treatment of angina - replacement of β-blockers in the presence of contraindications to their purpose or the occurrence of side effects when they are used, dihydropyridine - the second drug in the inefficiency of monotherapy β-blockers.

Other drugs. Metabolic preparations do not apply to first class drugs. According to the recommendations of the European Society of Cardiologists, they are given an auxiliary role in the treatment of angina, as they are added to the main anti-indant drugs.

Long monitoring of patients with angina. IBS is a chronic incurable disease that requires constant control. The fate of the patient depends on the quality of this control. According to the ASS / An Ax Recommendations, the patient must be carried out every 4-6 months during the first year after the diagnosis of angina. The surveys should then be carried out once a year with a stable state of the patient or urgently with the deterioration of the symptoms of the angina or the appearance of signs of another pathology.

With each meeting, the patient with angina need to receive an answer to the next 5 questions.

1. Did the level of physical activity decreased compared to the last visit?
2. Did it increased by the frequency of angina or its severity? If this happened or the patient reduced the level of physical activity so as not to provoke angina, treatment must comply with the principles of treatment of unstable angina.
3. How does the patient carry treatment?
4. Are there any successes in eliminating risk factors (especially arterial hypertension, diabetes and hyperlipidemia)?
5. Did the patient develop a new disease in the past period and does the accompanying pathology do not affect angularity?

What surveys should be carried out when monopardia observed?

1. Repeated ECG when using preparations that can affect conduction when changing the nature of pain syndrome, heartbeat or interruptions in heart activities.
2. X-ray in the patient with the occurrence of the CH clinic or its aggravation.
3. EchoCG with the definition of FV and segmental contractility in the occurrence of the CH clinic or its aggravation.
4. ECG - load testing in patients with changed pain syndrome in the absence of ECG anomalies (WPW syndrome, ST Depression more than 1 mm alone or full blockade of LPG).
5. In the presence of ECG anomalies specified in paragraph 4 - radionuclide testing. When revascularizing in history, as well as dubious ECG testing data.
6. Coronaryography in patients with angina 3 FC despite the maximum drug therapy.

1.3.Klinic pharmacokineti (main kinetic pro-trays, concepts of bioavailability, distribution, constants of absorption and elimination, therapeutic windows, etc. Intera-Vie drugs and food)
If pharmacodynamic mechanisms can be studied in animal experiments or in vitro. on isolated cultures of cells and tissues, then

clinical pharmacokinetics- the second important

next section of clinical pharmacology,

the data obtained only with the participation of a person. This section studies with a quantitative and high-quality side of all pro-processing and transformation of the drug in a healthy and sick organism and identifies the patterns between the concentration of the drug and the observed effects. The main pharmacokinetic process is:
A) release of medicine from the drug
B) suction (absorption) c) distribution d) metabolism

E) excretion (excretion)

Understanding these processes allows you to choose the optimal path of drug administration, it is possible to dose the drug, predict the scope of the offensive and the severity of the pharmacodynamic effect, its duration, assess the likelihood of unwanted phenomena, especially toxic, rationally compile drug combinations. The ability to use pharmacokinetic processes in practice is of particular importance in analyzing the failure of pharmacotherapy, as well as in the treatment of patients with severe functional impaired hearts, liver, kidney, etc. These processes are described by a number of quantitative parameters, the most significant of which are are:
Area under the pharmacokinetic curve (AUC) "Concentration-time" –
the integral parameter is proportional to the total number of HC in the body. According to this, the show can be judged both about the maximum concentration of the drug in the blood and the speed of its receipt and removal from the body.
Bioavailability (F) it shows which part of the LAN (%) during the output administration reaches the systemic blood flow and the speed with which this process occurs.
Absolute bioavailabilityit is defined as the AUC ratio of the drug introduced by the IS-followed method (orally, intramuscular, but), to AUC with its intravenous administration.
About relative bioavailability They say when comparing two different dosage forms one drug.
Total bioavailabilityreflects part of the dose of the drug, which when taken inside has reached systemic blood flow both in an unchanged form and in the form of metabolites formed in the pro-process of suction ("The effect of primary passage", preserved metabolism)
Absorption Constant (RAB) - characterized by
it is the rate of receipt of drugs in the systemic blood flow during the output administration.

Maximum concentration (Cmax) -

it characterizes the efficiency and safety of a le-cereal agent, its value should not be-going beyond the boundaries of the therapeutic range.

The time to achieve maximum

centers (Tmax) -with a linear dependence "concentration, effect" makes it possible to estimate the time for the onset of the maximum effect of the preparation. It should, however, it should be noted that for some drugs peak pharmacological

General provisions

actions may fall behind from the regimen of its maximum concentration.

Distribution volume (VD) - conditional
the clerk reflecting the seizure of the preparation of tedes from plasma or blood serum. Conditionally, this is the volume in which it is necessary to dissolve the entire dose of the drug to obtain concentration, equal to its plasma concentration.
Clearance (CL) -characterizes the speed of the "purge" of the body from the medicinal substance. This part of the apparent distribution volume, which is freed from the drug per unit of time. Allocate common, renal and end-check clearance, depending on the paths of the elimi-nation of the drug.

Elimination Speed \u200b\u200bConstant (KEL) -

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

Half-life (T½)- proportional

nilenna Elimination Constant (T½ \u003d 0.603 kel) And it shows for what time the concentration of the pre-parat in the body decreases twice.

Pharmacokinetic processes are closely related to the observed pharmacodynamic effects of drugs. First of all, this applies to the Naras pharmacological action drug with an increase in its dose. For most of the drugs, a high linear correlation rate between the level of medication in the blood and the clinical manifestation of the effect is installed. At the same time, this effect cannot increase infinitely with a constant increase in concentration and is limited to some physiological limit. In practice, it is necessary to use the reference material, which usually contains basic information on the rate of increment, severity and the duration of the effect of the drug dosing mode. These parameters are set during clinical trials of medicines in the large coat of patients. It is obvious that the rate of development and severity of the effect will be maximal with an intravascular administration of the drug, an alternative to which the sublingual reception can sometimes serve. However, part of the pre-paraty requires compulsory primary pro-walk through the liver, where it turns into its active form (most of the ACE inhibitors)

Pathological changes in the kosty-articular apparatus have arisen from our distant ancestors. And modern medicine leads disappointing facts: more than half of the population of our country (over 65 years old) suffer from diseases of the joints; One of them - arthrosis - does not affect only 3% of the elderly, the rest are faced with its manifestations. Rheumatoid polyarthritis in 5 years from the beginning of its development leads to a loss of ability to work. The main reason for this phenomenon is the lack of adequate treatment, so the International Protocol for the treatment of chronic joint diseases has been developed.

Pain as a permanent satellite of life

For almost every person with a diagnosis of polyarthritis, pain turns into a permanent satellite of life. Most often, painses are associated with the development of inflammation of the inner layer of the articular bag, which covers the surface of all elements forming the joint (including tendons), except for cartilage sites. The main functions of this layer are the nutrition of cartilage, depreciation and protection of the joint cavity from infection inwards.

Studies show a sad picture:

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

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

Official standards of pharmacotherapy

The first problem, on the solution of which the links of the chain of correctly selected therapy are directed - removal of pain. In traditional pharmacological practice, analgesics and non-steroidal anti-inflammatory means are used for this purpose.

First link: anti-inflammatory therapy

Inflammation of the joint proceeds with the release of specific proteins (inflammation mediators), which cause the decay of the articular tissues and the appearance common symptoms: Increased body temperature, fatigue, weakness. NSAIDs suppress the synthesis of these proteins and improve overall well-being. The following drugs are usually prescribed:

• diclofenac;
• indomethacin;
• pyroxics;
• ibuprofen.

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

• damage to the gastrointestinal tract, the ability to provoke erosion and bleeding formation;
• 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 accompanying lung diseases, due to the ability to provoke the attacks of bronchospasm;
• slowing down the processes of recovery of the cartilage layer of the joint;
• enhance arterial pressure.

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

The preparations of a new generation (the so-called selective inhibitors of COG2) are able to suppress the synthesis of proteins provoking inflammation not only in the joints, but also other organs and tissues, in particular vessels. At the same time, they have a number of advantages over their predecessors:

• significantly less often cause the development of secondary pathology by the digestive system;
• do not have a negative impact on the synthesis of new cells of the chisstava cartilage tissue;
• do not destroy kidney fabrics;
• the processes of formation of cells that destroy bone tissue are inhibited, therefore, are especially effective in concomitant osteoporosis;
• can be used in patients with arterial hypertension, since they do not have a significant impact on the increase in the figuration of blood pressure;
• they can be used for a long time as the main pharmaceutical agent in patients with deforming osteoarthritis, with severe resistant pain syndrome.

However, many attending doctors persistently continue to treat polyarthritis drugs from another NSAID group, adhering to outdated treatment standards. In addition, there are unreasonable assumptions about the negative impact. selective inhibitors COG 2 on the state of the cardiovascular system and their ability to cause a liver disruption. Recent studies prove the failure of such statements.

The main representatives of this group of drugs:

• nimesulide;
• meloxicam;
• kebrex (celecoxib);
• ropecoxib;
• etodolac;
• tsimikoxib and other cocksibi;
• langnoksikov.

However, when taking even the most effective of these funds, it is necessary to find an optimal dose, since small quantities lead to defects, and too large doses are toxic. Nimesulide (Naz) is most effective in a daily dosage of 200 mg; Meloxico - 15 mg, Kebreks - 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 an anesthetic agent, and the course of receiving the NSAID should go to the background and to be as short as possible. But taking into account the fact that the polyarthritis is a long-term disease, which is accompanied by constant inflammation of the articular elements, many specialists are still removing non-steroidal anti-inflammatory drugs on 1 place.

The most famous drugs among the drugs used: Cathadolon, Ropyrin and Butadion. Last Preparation Also available in the form of ointments, which allows it to be used locally in the lesion focus.

Third links: chondroprotectors

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

The fundamental difference in the effects of the reception of one of the above components is not, since they are closely related in the body: glucosamine stimulates chondroitin production, and chondroitin, decaying, forms glucosamine. Both of these tools allow not only to slow down the decay of cartilage sucks of the joint, but also partially restore them. In addition, it is proved that these drugs have an anesthetic and anti-inflammatory effect. The anti-inflammatory properties of chondroitin make it possible to consider it as a promising drug for the treatment of diseases that are not related to the musculoskeletal system.

The main drugs of this group:

• teraflex (complex drug);
• chondroitine sulfate;
• dona (glucosamine-based monopreparation);
• armor.

All of them must be accepted for a long time, since the first effect is manifested only a month later from the start of reception.

Fourth link: Mioryelasanta

These drugs eliminate reflex muscle spasms As one of the factors provoking the development of pain syndrome. They approximately 1/4 increase the therapeutic activity of nonsteroidal anti-inflammatory funds.

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

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

The relaxants of the central type of action are mainly used: Sirdalud, Middokalm, Baclofen, Tranksen, diazepam. All of them possess wide spectrum side effects: cause drowsiness, muscle weakness, dry mouth, lower arterial pressure. Sirdalud and Middokalm are considered the most soft preparations.

Folk remedies as an addition to the main treatment

Folk Medicine offers a wide variety of means for treating polyarthritis. The most effective of them are funds of api and phytotherapy.

Popular among patients with polyarthritis treatment with compresses or rubbing various alcohol tinctures. It's really good way Remove pain and slightly reduce inflammation, however, it should be remembered that the effective pathogenetic treatment of the polyarthritis. People's medicine cannot be offered anyway. Therefore, its methods can only be used together with a traditional treatment scheme.

It should not be forgotten that traditional medicine often uses vegetable raw materials. And modern environmental conditions Forcing deeply doubt its quality and safety of the current components.

Be sure to consult a doctor before treating diseases. This will help take into account individual tolerability, confirm the diagnosis, make sure that the treatment and eliminate the negative interactions of drugs. If you use recipes without a consultation with your doctor, then it is completely for your fear and risk. All information on the site is presented for informational purposes and is not a healing benefit. All responsibility for use 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 by the number of titles and doses and at the same time adequate the severity of the disease in order to have an effective help to the suffering person.

Pharmacotherapy should be effective. Provide in certain clinical situations a successful solution of the tasks of treatment. The strategic objectives of pharmacotherapy can be different: a cure (in a traditional understanding), a slowdown in the development or relief of exacerbation, prevention of the development of the disease (and its complications) or the elimination of painful or prognostic adverse symptoms. In chronic diseases, medical science determined the main purpose of the treatment of patients with control over the disease when good quality Life (i.e., subjectively good condition of patient, physical mobility, lack of pain and discomfort, ability to serve itself, social activity).

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

Physical mobility;

No pain and discomfort;

Ability to serve itself;

The ability to normal social activity.

Purpose drugs It is impossible to conduct "just in case", without certain testimony.

The risk associated with the reception of medicines has become the main medical problem over the past 40 years. This concern increased after unfortunately with talidomide in 1960-61, when after taking it with pregnant women, children who terrified the world were born with their ugliness. It was exclusively a dramatic example of all medicinal therapy practices.

The following pharmacotherapy varieties are distinguished:

1.Thethiotropic (elimination of the causes of the disease).

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

3. Pricing (compensation of a lack of vital organism).

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

5. Finding (restoration of disturbed units of the adaptation system of the body).

6.Profilactic (preventing the development of the acute process or exacerbation of chronic).

For acute disease Most often, treatment is starting with etiotropic or pathogenetic pharmacotherapy. With exacerbation of chronic diseases, the choice of pharmacotherapy species depends on the nature, severity and localization of the pathological process, the age and gender of the patient, the state of its compensatory systems, in most cases the treatment includes all types of pharmacotherapy.

Before starting pharmacotherapy, it is necessary to determine the need for it.

If intervention during the disease is necessary, the drug can be prescribed under the condition that the probability of its therapeutic effect is greater than the probability of the undesirable consequences of its use.

Pharmacotherapy is not shown if the disease does not change the quality of the patient's life, its projected outcome is not dependent on the use of drugs, as well as if irrevocating methods of treatment are effective and safe, more preferable or inevitable (for example, the need for an emergency surgery).

One of the most important principles of clinical pharmacology is to prescribe a medicine when there is indications for this.

The appointment of "just in case" the vitamins of the group in the allergenic properties that have a number of people increase the number of anaphylactic reactions.

Increased temperature - This is a protective response of the body, and in the overwhelming number of cases at temperatures below 38 with the purpose of the antipyretic is not required.

"Passchables in the town" was the routine appointment of antibiotics in viral diseases from the first day of the disease for the "prevention of secondary infection".

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

At the same time, it is worth paying attention to the reputation of the firm producing medication, since the same drugs produced by different firms may have serious qualitative differences.