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

N.N. Bezyuk, Ph.D., Department of Faculty Therapy No. 1 of the National medical university them. A.A. Bogomolets, Kyiv

How important is the problem of angina pectoris?

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Drug treatment of angina aimed at preventing MI and death

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Antagonists Sa. There has been a decrease in the importance of this class of antianginal drugs. Initially wariness towards them when treatment of ischemic heart disease has been associated with the use of short-acting drugs as monotherapy, as they increase the incidence of coronary events and mortality.

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

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

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

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

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

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

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

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

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

Federal guidelines for the use of drugs

The publication contains recommendations, taking into account evidence-based medicine, 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.).

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

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

principles of rational pharmacotherapy

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

For the rational selection of medicines, there are four criteria developed by the World Health Organization (WHO), by which the whole pharmacological groups, and separate medications:

· Efficiency

· Safety

· Eligibility

· Price

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

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

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

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

5. It is necessary to inform the patient about the goals and duration of treatment, expected results, the principle of action of prescribed medications, warn about possible side effects and their recognition. interaction of drugs with alcohol, effect on driving, etc. The regimen for taking medications should be discussed (and written down!) in detail, indicate the time and method of taking the medication, and the patient’s actions in case of forced or accidental skipping of a dose.

6. You should strive to ensure that the desired therapeutic effect is achieved with the smallest effective dose of the drug.

7. Dosing tactics (gradual increase in dose, impact dose with transition to maintenance doses, stable maintenance dose, gradual dose reduction, etc.) depend on the specifics of the drug used and the clinical situation.

9. An adequate assessment of the results of dose adjustment is possible no earlier than after 4 half-lives of the drug, provided that it is taken regularly (it is also necessary to make an adjustment for the timing of the development of the pharmacological effect).

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

11. It is necessary to develop a high level of adherence to the prescribed treatment in the patient.

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

the federal law“On the circulation of medicines” dated April 12, 2010 N 61-FZ (current edition, 2016)

1. This Federal Law regulates relations arising in connection with circulation - development, preclinical research, clinical trials, examination, state registration, standardization and quality control, production, manufacturing, storage, transportation, import into the territory Russian Federation, export from the territory of the Russian Federation, advertising, release, sale, transfer, use, destruction of medicines.

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

Nanotechnology is a field 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 a scale of 100 nm or less, the classical physical laws of interaction between atoms and molecules are replaced by quantum ones, for example, tunnel transitions and surface plasma resonance (SPR). A system with dimensions in the nanometer range can be described from the perspective of the thermodynamics of nonlinear processes. The overall effect of nanotechnology in pharmacology is fundamental 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 associated with a nanostructure membrane 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. degradation of the nanostructure does not occur immediately, but over a certain time, and its effect is cumulative;

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. The pharmacokinetic parameters for each specific drug packaged in nanostructures vary significantly.

Targeted drug delivery systems (DDS) - a liposome equipped with a “molecular compass” (antibodies that help find the affected organ) reflect nanotechnological approaches. Drug delivery using monoclonal antibodies to solve targeted drug delivery can significantly improve the quality of life of patients by reducing side effects, as well as increasing selectivity, and therefore the effectiveness of treatment. Nanotechnologies make it possible to perform microscopically precise operations for the destruction of pathological foci. To do this, metal nanoparticles with drugs and antibodies fixed on them are introduced into the body. With the help of specific antibodies, nanostructures that act as a “molecular compass” unmistakably identify targets for action on pathologically altered cells, attach to them through the antigen-antibody reaction and destroy them using the transported drug (anti-blastoma antibiotics). Nanoneuropharmacology involves the use of drugs in new dosage forms - nanostructures with neurotropic effects that have the properties to correct the function of the central nervous system (liposomes, fullerenes, dendrimers, nanoclusters, nanotubes and others). A method for the biochemical synthesis of metal nanoparticles (Ag, Au, Cu, Zn, Co, Ni and others) has been developed. Standardized nanoparticles (15 nm) remain stable 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 beneficial properties.

It is always necessary to evaluate the risk-benefit ratio, since the use of any drug is associated with certain risks.

The response to pharmacotherapy depends both on the characteristics of the individual patient and on his behavior, habits (consuming certain foods and nutritional supplements, following the prescribed dosage regimen), the presence of renal or liver failure, other concomitant diseases, and taking other medications. Prescription errors (choosing the wrong drug, misreading a prescription, taking a drug incorrectly) also affect the effectiveness of treatment.

Adherence to prescribed pharmacotherapy

Adherence is a measure of how strictly a patient follows a prescribed treatment plan. In the case of drug therapy, compliance with the prescribed regimen means obtaining the drug in a timely manner and taking it in strict accordance with the prescribed dose, frequency of administration and duration of treatment. Patients should be reminded that if they stop taking the drug or deviate from the prescribed dosage regimen, they should inform their doctor, which rarely happens in practice.

Only about half of patients take their medications as prescribed by their doctor. Most common reasons lack of adherence to pharmacotherapy are:

• the need for frequent use;
• denial of the presence of the disease;
• lack of understanding of the benefits of drug therapy;
• cost of treatment.

There are other reasons. Children are less likely to adhere to the prescribed treatment regimen. The lowest compliance is observed in chronic diseases that require complex long-term treatment. Parents may not fully understand the instructions for using medications and, after 15 minutes, forget half the information received from the doctor.

Elderly patients adhere to treatment to the same extent as other adult patients. However, factors that reduce compliance (eg, financial difficulties, use of multiple medications or medications requiring multiple doses per day) are more common among older patients. Cognitive impairment may further reduce compliance. Sometimes the doctor prescribing the drug is forced to use a creative approach when choosing a drug, prescribing the easiest-to-use available analogue. For example, patients with hypertension who have difficulty taking oral medications may be prescribed clonidine as a transdermal therapeutic system, which should be replaced weekly by a nurse or family member.

The most obvious result of non-adherence to prescribed therapy is the failure to improve the patient's condition or achieve a cure. It is believed that this circumstance annually leads to 125,000 deaths among patients suffering from cardiovascular diseases. Patient adherence to prescribed therapy could prevent up to 23% of nursing home admissions, up to 10% of hospitalizations, many doctor visits, diagnostic studies and many types of unnecessary treatment in this case. In some cases, decreased compliance may lead to increased disease severity. For example, skipping a dose or early cancellation of antibacterial or antiviral therapy contributes to the growth of pathogen resistance.

Pharmacists, pharmacy technicians, and nurses can help identify and resolve problems related to non-compliance with prescriptions. For example, a pharmacy employee may note that a patient does not return to refill a prescribed drug or does so prematurely. Discussing prescriptions prescribed by a doctor together with the patient, a pharmacy employee or nurse can identify and help address patient misunderstandings or concerns. The doctor can change the patient’s difficult or frequent drug regimen, or replace the latter with a safe, effective, but cheaper drug.

Errors in prescribing medications

Errors associated with the prescription of medications lead to an increase in the incidence of complications of pharmacotherapy.

Their main reasons:

• Wrong choice of medication, prescribing it in an inadequate dose, incorrect dosage regimen and/or duration of therapy.
• Misreading of a prescription by a pharmacy employee, resulting in the dispensing of the wrong drug or dosage.
• Misreading of the packaging by a pharmacy employee, resulting in the dispensing of the wrong drug or dosage.
• Incorrect instructions to the patient.
• Incorrect administration of the drug by a healthcare professional or patient.
• Improper storage of the drug by a pharmacy employee or patient, which leads to a decrease in its activity.
• The use of expired medications, which leads to a decrease in their activity.
• Incorrect use of medication by the patient.

Errors in prescribing medications are quite common, especially in certain categories of patients. The risk group includes elderly people, women childbearing age and children. Drug interactions are especially common in patients receiving multiple medications. To reduce risk, it is necessary to know all the medications the patient is taking (including those prescribed by other doctors and those sold without a prescription) and keep their list up to date. Patients need to be convinced of the need to draw up full list medications taken so that, if necessary, provide it to your doctor or other medical professional. The recipe should be written as clearly as possible.

Some drug names are similar, which can cause confusion if they are written illegibly. Deciphering some traditional symbols that may be misread helps to avoid mistakes. For example, “1 r/d” can easily be confused with “4 r/d”, so it is preferable to write “once a day”. Using printed recipes helps avoid problems associated with illegible handwriting or incorrect abbreviations.

Errors in prescribing medications are also possible in medical institutions. In particular, the drug may be given to the wrong patient at the wrong time, or the wrong method of administration may be mistakenly prescribed. Some drugs must be administered slowly intravenously; some cannot be entered in parallel. If such errors are detected, you must immediately inform your doctor and consult a pharmacist. Electronic drug dispensing systems reduce the likelihood of such errors.

Drugs should be stored in such a way as to ensure that their activity is maintained. Pharmacies that distribute drugs by mail must also follow the necessary transportation regulations. Often, medications are not stored correctly by patients, which increases the likelihood that they will lose their effectiveness long before the expiration date. The packaging should clearly indicate whether the drug should be stored in the refrigerator or in a cool place, protecting it from exposure high temperatures or sunlight, or observing special storage conditions. On the other hand, unnecessary precautions reduce the likelihood of adherence to the prescribed treatment regimen and waste the patient's time. For example, unopened insulin should be stored in the refrigerator; however, the opened bottle can be stored for a long time outside the refrigerator, in a place that does not expose it to excessively high temperatures or direct sunlight.

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

Most often, errors occur when patients do not have information about how to take the drug correctly. As a result, they may mistakenly take the wrong drug or the wrong dose of the drug. Therefore, patients should receive information about what dose of the drug to take and why this particular drug was prescribed. It is advisable that this information be kept in writing by the patient. It should also be recommended to consult a pharmacy employee about the use of the drug. The packaging should be convenient but safe. If there is no likelihood of children having access to the medicines and the patient has difficulty opening the container with the medicine, simple packaging without child-resistant mechanisms should be used.

Drug interactions

Drug interactions- this is a change in the effects of a drug due to recent or simultaneous use of two or more drugs (drug-drug interactions) or taking the drug with food.

Drug interactions may result in increased or decreased effect of one or more drugs in the combination. Clinically significant interactions are often predictable and usually undesirable because may lead to side effects or lack of therapeutic effect. Less often, clinicians can use predictable drug-drug interactions to achieve what they want therapeutic effect. For example, the simultaneous administration of lopinavir and ritonavir to a patient with HIV leads to a slowdown in the metabolism of lopinavir and an increase in its plasma concentration, which increases the effectiveness of therapy.

When two drugs with similar properties are taken simultaneously, their effects may be additive. For example, if a patient takes one benzodiazepine as a tranquilizer and another as a sleeping pills at night, their cumulative effect can lead to toxicity.

Drug interactions are divided into:

• to pharmacodynamics,
• pharmacokinetic.

In a pharmacodynamic interaction, one drug changes the body's sensitivity or response to another, having a similar (agonistic) or opposite (antagonistic) effect. These effects are usually realized at the receptor level, but can also arise as a result of influence on intracellular systems.

In pharmacokinetic interactions, one drug in the combination usually alters the absorption, distribution, protein binding, metabolism, or elimination of the other. Accordingly, the amount and duration of exposure of the first drug to the receptor changes. Pharmacokinetic interactions change the severity and duration of the effect, but not its type. Often, it can be predicted based on the characteristics of individual drugs, or identified by monitoring their concentrations or clinical symptoms.

Minimizing drug-drug interactions. The attending physician must know about all medications that the patient is taking, incl. prescribed by other specialists, sold without a prescription, as well as food additives. It is advisable to ask the patient about his diet and alcohol consumption. The minimum amount of the drug should be prescribed at the minimum effective dose for the shortest period of time. It is necessary to determine the effects (desired and side effects) of all medications taken, since they usually include a spectrum of potential drug interactions. To avoid toxicity due to unpredictable drug interactions, drugs with a wider therapeutic range should be used.

Patients should be monitored for the development of adverse reactions, especially after changes to the treatment regimen; some types of interactions (for example, as a result of enzyme induction) may appear a week or later. Drug interactions must be considered as possible reason any unforeseen complications. If an unexpected clinical reaction occurs, the physician may need to determine the serum concentrations of individual drugs being taken. Based on this information, as well as obtaining relevant information in the literature or from an expert clinical pharmacologist, it is possible to adjust the dose until the desired effect is achieved. If dose adjustment is ineffective, the drug must be replaced with another drug that does not interact with those the patient is receiving.

Pharmacogenetics

Pharmacogenetics is the study of differences in pharmacological response depending on the genetic makeup of the organism.

The activity of drug metabolizing enzymes often varies widely among healthy people. As a result, the rate of elimination of a particular drug can differ tens of times. Most of these differences are caused by genetic factors and aging.

Genetically determined changes in drug metabolism (for example, caused by different activities of enzymes that carry out its acetylation, hydrolysis, oxidation or other transformations) may have clinical consequences. For example, patients who rapidly metabolize certain drugs may require higher doses or more frequent dosing to achieve therapeutic drug concentrations in the blood. At the same time, patients who slowly metabolize certain drugs, in order to avoid intoxication, may need to be prescribed the drug in smaller doses with a smaller frequency of administration, in particular, this applies to drugs with a small breadth of therapeutic action. For example, in patients with inflammatory diseases intestines requiring azathioprine, thiopurine methyltransferase (TPMT) genotyping is performed to determine the optimal starting dose of the drug. Most genetic differences cannot be predicted before drug administration, but for an increasing number of drugs (eg, carbamazepine, clopidogrel, warfarin), variability, efficacy, and risk of toxicity may be associated with certain genetic differences. In addition, there may be an interaction between environmental factors and the patient's body, which leads to a change in response to drug therapy.

Placebo

Placebo is an inactive drug or intervention often used in controlled trials to compare with potentially active drugs.

The term placebo (Latin for “I will like you”) originally referred to inactive, harmless substances that were given to patients to improve their well-being under the influence of suggestion. Later, sham interventions (eg, sham electrical stimulation, simulated surgical procedures) were also classified as placebos. The term is sometimes used to refer to active drugs prescribed solely as a placebo for conditions for which they are not actually effective (for example, an antibiotic for patients with a viral infection). Manifestations of the placebo effect are often subjective (for example, headache, nausea) rather than an objective nature (speed of wound healing, degree of infection of burns).

Effects. Although placebos are physiologically inactive, they can have real effects, either positive or negative. These effects are typically associated with the expectation that the drug will work; The anticipation of the occurrence of unwanted reactions is sometimes called the nocebo effect. The placebo effect usually occurs with subjective responses (eg, pain, nausea) rather than objective ones (eg, rate of ulcer healing, infection rate of burn wounds).

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

• showing confidence in a positive effect on the part of the doctor (“this drug will make you feel much better” versus “there is a chance that it will help you”);
• patient expectations (the effect is greater if the patient is confident that he is receiving the active substance than when he knows that he may be receiving a placebo);
• type of placebo (substance for intravenous administration have a greater effect compared to those taken orally).

The placebo effect does not occur in all patients, and it is impossible to predict in advance who will experience it. The relationship between personality traits and placebo response has been discussed many times, but is not really well established. However, patients who feel strongly dependent on or eager to please the physician are more likely to experience positive effects; expressive individuals are more likely to report effects, both positive and negative.

Use in clinical research. Many clinical studies compare the effect of active treatment with placebo. The estimated placebo effect must then be subtracted from the total observed effect to determine the true treatment effect. In other words, clinically and statistically significant differences need to be assessed. In some studies, placebos improve symptoms in a significant proportion of patients, making it difficult to determine the effect of active treatment.

Use in clinical practice. In rare cases, a placebo may be prescribed when the doctor determines that the patient's illness is mild and does not require the use of active drugs, or when effective treatment absent in principle (for example, in the case of nonspecific malaise, fatigue). This is often justified on the grounds that it satisfies the patient's desire to receive treatment without putting him or her at risk. adverse reactions and in some cases, making you feel better (due to the placebo effect or spontaneous improvement).

Ethical considerations. In clinical trials, the subject of ethical discussion is the permissibility of using placebos as such. When effective treatment exists (eg, opioid analgesics for severe pain), it is generally considered unethical to deprive study participants of treatment by assigning a placebo. In such cases, control groups of patients receive standard active treatment. Because study participants are aware in advance that there is a possibility of receiving a placebo, there is no concern about intentional deception.

However, when a patient is prescribed a placebo in real-world clinical practice, they are not told that they are receiving an inactive treatment. In this case, the ethics of misleading the patient becomes moot. Some clinicians consider this approach to be inherently unethical and, if known, harmful to the physician-patient relationship. Others argue that it is much more unethical to not give a patient any treatment, thereby depriving him of the opportunity to feel better. Prescribing a pharmacologically active drug to a patient solely as a placebo can also be considered contrary to the principles of bioethics, since in this case the patient is exposed to possible risk real side effects (as opposed to nocebo effects).

New drug research

Potential drug substances can be found by large-scale screening of hundreds or thousands of molecules for biological activity. In other cases, knowledge of the specific molecular aspects of the pathogenesis of a particular disease allows the use of a rational approach to the creation of new drugs through computer modeling or modification of existing pharmacologically active molecules.

In early preclinical studies, potentially active compounds are studied in animals to evaluate desired effects and toxicity. Substances that have demonstrated their effectiveness and safety become candidates for further study in humans. In the United States, the protocol describing the clinical trial must be approved by the appropriate Institutional Review Board and the US Food and Drug Administration (FDA), which then grants approval for the new drug to be studied. From this moment, the patent period for the drug begins, usually giving the owner exclusive rights for the next 20 years; however, the drug cannot be released to market without FDA approval.

The phase 1 clinical trial evaluates the safety and toxicity of the drug in humans. To do this, various doses of the test substance are taken by a small number (usually 20 to 80) of healthy volunteers (usually young men) to determine the dose at which the first signs of toxicity occur.

The goal of phase 2 is to confirm the drug's activity in a specific pathology. The drug being studied is prescribed to a group of up to 100 patients for the treatment or prevention of this pathology. An additional objective of this phase is to determine the optimal dosing regimen.

Phase 3 studies evaluate the effect of a drug in larger (100 to several thousand people) and heterogeneous groups of patients to confirm the feasibility of clinical use of the drug being studied. This phase will also compare the drug with existing standard treatment regimens and/or placebo. Practitioners and many health care settings may be involved in the study. The main goal of this phase is to confirm the effectiveness of the drug and its possible effects (both positive and negative), which may not be identified in phase 1 and 2 studies.

When sufficient data has been collected to register the drug, the materials are submitted to the regulatory organization, which gives permission to release it on the market. From the early stage of drug development to registration, it often takes about 10 years.

Phase 4 studies are conducted after a drug is approved and marketed. Such studies are usually ongoing and involve large patient populations. Often, such studies include special subgroups of patients (eg, pregnant women, children, elderly patients). Phase 4 studies also require regular reporting of adverse events that occur while using the drug. Some drugs approved by the FDA after Phase 3 were subsequently withdrawn from the market after new serious side effects were identified in Phase 4.

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

Topic 1. Basics of pharmacotherapy

Target: know the methodology of the subject.

Plan:

The concept of pharmacotherapy as a science.

Types of pharmacotherapy.

Basic concepts and terms of pharmacotherapy.

The tasks and significance of pharmacotherapy in medicine and pharmacy.

Ways of introducing drugs into the body.

Types of action of drugs

Compatibility of drugs.

Features of pharmacotherapy in children and the elderly.

Pharmacotherapy in elderly and senile people.

Features of pharmacotherapy in pregnant women and nursing mothers.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Her tasks:

1) testing new pharmacological agents;

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

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

4) information support and advisory assistance to medical workers.

Resolves issues such as:

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

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

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

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

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

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

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

4) monitoring the effect of the drug;

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

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

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

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

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

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

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

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

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

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

pharmacokinetics study;

determination of acute and chronic toxicity;

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

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

Table1. Good Pharmaceutical Practice Standards

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

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

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

Table 2. Clinical trial phases

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

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

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

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

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

Adverse reactions and complications are possible when taking any medications.

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

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

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

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

2) toxic complications, regardless of dose;

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

4) allergic reactions;

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

There are several types of antagonism:

Physico-chemical, based on the absorption of poisons

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

Chemical, based on the interaction of substances,

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

Physiological, based on the administration of drugs,

exerting the opposite effect on a given organ or tissue

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

There are also:

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

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

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

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

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

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

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

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

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

Showing high biological activity in very small doses, vitamins are needed:

For normal cellular metabolism and tissue trophism

For energy transformation

For plastic exchange

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

To ensure the body's immunological reactivity

For the normal functioning of all organs and tissues.

Pharmacotherapy is inextricably linked with toxicology.

WAYS OF ADMINISTRATION OF MEDICINES INTO THE BODY

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

Enteral routes of administration

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

Main principle 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 help to the suffering person.

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

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

Physical mobility;

No pain or discomfort;

Ability to serve oneself;

Ability for normal social activity.

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

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

The following types of pharmacotherapy are distinguished:

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

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

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

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

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

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

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

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

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

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

One of the most important principles clinical pharmacology– prescribe medication when there is indication for it.

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

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

The routine prescription of antibiotics for viral diseases from the first day of illness to “prevent secondary infection.”

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 with lethal antibiotics, it was found that in 60% of cases there were no indications for their use.

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