Principles of rational pharmacotherapy. Pharmacotherapy of rheumatoid arthritis from the standpoint of evidence-based medicine: new recommendations Mistakes in prescribing drugs

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

10.1. TYPES OF PHARMACOTHERAPY

There are several types of pharmacotherapy:

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

Pathogenetic (affects the development of the disease);

Substitutive (introduced medications compensate for vital substrates, the synthesis of which in the body is difficult or absent);

Symptomatic (blocks individual syndromes or symptoms that aggravate the life of the patient);

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

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

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

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

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

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

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

10.2. GOALS AND OBJECTIVES OF RATIONAL PHARMACOTHERAPY

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

Determination of indications for pharmacotherapy;

Choice of drugs or combinations of drugs;

The choice of routes and methods of administration, dosage forms;

Determination of the individual dose and dosing regimen of drugs;

Correction of drug dosing regimens in the course of pharmacotherapy;

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

Justification of the timing and duration of pharmacotherapy;

Determination of indications and technology of drug withdrawal. The first question that arises when prescribing treatment is

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

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

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

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

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

10.3. STAGES OF RATIONAL PHARMACOTHERAPY

The tasks of pharmacotherapy are solved in stages.

Diagnosis and determination of the severity of the patient's condition.

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

The choice of the type of pharmacotherapy for this patient.

LAN group selection. It is carried out according to the leading or main disease (syndrome), the goals and objectives of treating a particular patient are formulated, based on the nosology or syndromes, the severity of the course and severity of the disease, knowledge of the general principles of treatment of this pathology, possible complications, previous drug and non-drug therapy. Accepted during

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

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

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

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

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

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

It is more difficult to concretize and choose control parameters during therapy with metabolic drugs. In these cases, the evaluation of the action of drugs can take place indirectly using evidence-based medicine or meta-analysis techniques. In order to prove the effectiveness of trimetazidine in the treatment of coronary heart disease, it was necessary to conduct a multicenter prospective study and evaluate the feasibility of using this drug (reducing the incidence of coronary heart disease complications in the study group compared to the control group).

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

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

10.4. PHARMACOLOGICAL HISTORY

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

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

any information, there is no need to refuse this drug. It should be used at a lower dose and in a different dosage form.

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

10.5. CHOICE OF DRUG AND DOSAGE REGIME

In recent years, treatment often begins with regulated drugs. Regulated drugs of first choice for many common diseases are well known. First choice drugs are included in the state list of essential drugs, indicated in the formulary of the medical institution and offered in the approved standard treatment regimens for the category of patients under consideration.

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

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

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

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

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

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

Higher doses are necessary when the bioavailability of the drug is reduced, the patient's low sensitivity to it, as well as when using drugs with competitive properties and drugs that accelerate the metabolism or elimination of this drug.

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

Doses of drugs with the ability to material and functional cumulation may be different at the beginning of treatment (initial dose, loading dose) and throughout it (maintenance dose). For such drugs, initial dosing schemes are being developed that provide for a different rate of onset of the effect depending on the rate of saturation (cardiac glycosides, etc.).

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

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

10.6. PHARMACOLOGICAL TEST

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

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

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

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

In modern functional diagnostics often used pharmacological tests:

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

Echocardiography with a nitroglycerin test (may provide information on the reversibility of restrictive diastolic dysfunction of the left ventricle);

ECG with atropine test (used to distinguish between bradycardia associated with the influence vagus nerve and bradycardia due to organic myocardial damage);

The study of the function of external respiration with a sample of β 2 -agonists (used to detect reversible bronchial obstruction).

A pharmacological test is carried out with drugs that have a “first dose” effect or a clear relationship between concentration and pharmacological effect. This technology is inappropriate and is not carried out when using chemotherapeutic drugs (drugs) with a long latent period pharmacological action.

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

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

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

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

10.7. DOSE TITRATION

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

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

10.8. CONTROL OF EFFICIENCY AND SAFETY

WHEN CARRYING OUT PHARMACOTHERAPY

When conducting long-term or permanent pharmacotherapy, treatment is monitored according to an individual program designed to provide effective and safe individualized pharmacotherapy.

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

Criteria characterizing the stabilization of the condition in this patient;

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

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

The expected time of onset of the maximum therapeutic effect;

The time of onset of stabilization of clinical indicators;

Criteria for dose reduction or discontinuation of the medicinal product due to the clinical effect obtained;

Indicators, the change of which may indicate the escape of the effect of the therapy;

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

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

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

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

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

Particular attention should be paid to the dosing regimen during long-term therapy with drugs with a small therapeutic latitude. In such cases, only drug monitoring can avoid severe adverse reactions.

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

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

functionality of the patient. This can be detected using certain objective tests (eg, increased range of motion of the affected joint after taking an analgesic, changes in behavior and intellectual performance after the use of antidepressants).

Criteria for the effectiveness or undesirable action of drugs - changes in the patient's condition, which are due to the use of this drug. For example, a convincing indicator of the anticoagulant effect of heparin is the prolongation of blood clotting time. It is impossible to ignore the opinion of the patient about the action of drugs. In some syndromes, it may be leading in evaluating the effectiveness of the drug (for example, pain syndrome and its relief).

10.9. PATIENT ADMISSION TO TREATMENT

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

Lack of trust or lack of trust in the doctor;

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

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

A complex scheme for taking drugs;

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

Improving well-being (the patient may prematurely stop treatment or change the regimen for the use of drugs);

Development of unwanted drug reactions;

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

The cost of the medicine and the financial situation of the patient. Unsatisfactory adherence of the patient to the appointment of drugs

(for example, unauthorized withdrawal of drugs) can lead to unwanted drug reactions, up to severe, life-threatening complications. Dangerous and unauthorized change of dosing regimen

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

Patient adherence to treatment can be improved by clarifying the following points:

Clearly indicate the name of the drug;

Clearly explain the purpose of taking drugs;

Indicate the estimated time of the expected effect;

Give instructions in case of missed drug intake;

Specify the duration of treatment;

Explain how to detect adverse drug reactions;

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

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

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

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

10.10. FEATURES OF PHARMACOTHERAPY OF URGENT CONDITIONS

The doctor experiences great difficulties when carrying out pharmacotherapy in urgent situations, when the patient has depletion of functional systems and paradoxical reactions to administered drugs may occur, which increases the risk of developing NDL. In such a situation, pharmacotherapy requires the doctor to have deep medical knowledge, efficiency in choosing and using adequate doses of drugs.

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

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

10.11. FEATURES OF LONG-TERM PHARMACOTHERAPY

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

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

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

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

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

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

In some diseases, as well as congenital and acquired pathological conditions, there is a need for maintenance pharmacotherapy for a long time, sometimes for life. This takes place in the following cases:

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

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

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

At the 4th stage, the ongoing pharmacotherapy is corrected if it is not effective enough or if new complications of the disease appear.

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

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

Increasing the dose of the drug (clonidine);

Replacing the drug with a new drug;

Transition to combination therapy.

The need for correction of pharmacotherapy may arise when the clinical condition stabilizes. In this case, it is necessary to either cancel the drug, or switch to maintenance therapy. At the same time, it should be borne in mind that some drugs require a gradual dose reduction, these include: amphetamine, antidepressants, anti-

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

10.12. ERRORS IN ACTION EVALUATION

MEDICINE

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

Psychotherapeutic effect similar to the placebo effect;

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

Restoration of impaired function not associated with treatment - regression of the pathological process, remission of the disease, cessation of exposure to pathogenic factors and the emergence of conditions for the inclusion of compensatory mechanisms.

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

10.13. WITHDRAWAL OF DRUGS

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

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

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

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

The manifestation of toxic or side effects of drugs, excluding the possibility of replacing the drug (digitalis intoxication with the use of cardiac glycosides).

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

With indications for withdrawal and the absence of contraindications to it, the doctor determines the necessary rate of withdrawal, taking into account changes in the body caused by the drug. To the greatest extent, this applies to drugs that act at the level of the regulatory system with feedback structures, primarily to hormones and means of mediator action. For example, the sudden withdrawal of clonidine in patients with arterial hypertension can be the cause of severe hypertensive crises.

The following options for canceling drugs are possible:

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

Cancellation by a gradual decrease in the daily dose in the time required for the regression of functional changes (for example, increased sensitivity of adrenoreceptors due to the use of sympatholytics) or to restore suppressed drug function;

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

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

10.14. COMBINED APPLICATION

MEDICINES

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

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

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

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

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

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

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

How important is the problem of angina pectoris?

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

The prevalence of angina pectoris in Ukraine increased by 64% compared to 1999 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 coronary artery disease in the structure of all causes of death in Ukraine is also 2 times higher than the average European indicators and US statistics (41%, 22% and 20%, respectively; British Heart Foundation. European Cardiovascular Disease Statistics 2000).

Sequelae of angina pectoris. The occurrence of angina leads not only to a deterioration in the quality of life (decrease in the tolerance of 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 increase in the risk of death. During the first year after the onset of angina pectoris, 10% of patients develop MI or they die, another 20% require revascularization (Gandhi M. et al., 1995). According to various sources, angina precedes 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, treatment costs, 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 pectoris, there were 2.35 million visits to the doctor, 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 pectoris is not diagnosed in a timely manner, this will lead to the fact that the patient will not receive adequate treatment that could improve the quality and duration of his life. The consequence will be the progression of symptoms and the development of complications (MI or death) in high-risk individuals. IHD is the cause of death of approximately every second inhabitant of our country.

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

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

The goal of treatment of stable angina pectoris. When embarking on the treatment of patients with stable angina, it must be clear that there are only two goals for treating patients with this diagnosis. The first is the prevention of MI and death, and therefore the extension of life. The second is a decrease in the symptoms of angina pectoris, which leads to an improvement in the quality of life. Naturally, treatment aimed at prolonging life is a priority. When there are two different treatments (drugs) that are equally effective in relieving the symptoms of angina pectoris, the treatment that prolongs life is preferred.

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

A necessary condition for effective treatment is also a good knowledge by the patient of the essence of his illness and understanding of the meaning of treatment. For most patients, the goal of treatment should be complete or almost complete elimination of anginal pain and a return to normal life and functional abilities, corresponding to functional class I angina pectoris. 82% of patients with stable exertional angina limit daily activities in order to avoid angina attacks, and seek to increase the time of sleep and rest. (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 multiple comorbidities, symptom relief may be sufficient to allow only limited exercise to be performed.

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

What are the current recommendations for the treatment of stable angina? We should follow the guidelines for the treatment of stable angina pectoris European Society cardiologists (ESC, 1997), their newer version, the American Heart Association guidelines (ACC/ANA, 2002), and the most recent version, the American College of Physicians guidelines (ACP, 2004). In the spring of 2005, new recommendations for the treatment of stable angina pectoris of the European Society of Cardiology were announced, as it is clear that the current ESC recommendations are already significantly outdated.

Medical treatment of angina to prevent MI and death

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

Clopidogrel, the only antiplatelet drug proven to be superior to aspirin in preventing MI, stroke, and vascular death, is growing in importance. The combination of aspirin and clopidogrel leads to an even greater increase in the effectiveness of treatment. There is a need for this in the case when the patient has already suffered any complication of atherothrombosis - acute coronary syndrome or stroke, as well as after coronary angioplasty. Dipyridamole should no longer be used in coronary artery disease, either alone or in combination, as it may induce myocardial ischemia (Patrono C. et al., 2004).

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

In the presence of bradycardia, dysfunction sinus node or AV blockade, β-blockers may cause symptomatic bradycardia or more high degree blockade. In addition, β-blockers are contraindicated in patients with bronchial asthma. In patients with obstructive pulmonary disease, insulin-dependent diabetes mellitus, and severe vascular disease lower extremities treatment should begin with very small doses.

The higher the patient's heart rate at rest, 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 the use of β-adrenergic blockers is their appointment in doses that provide a distinct effect of blockade of β-adrenergic receptors. To do this, it is necessary to achieve a decrease in heart rate at rest to 55-60 per minute, which is not always achieved in real clinical practice and is accompanied by an insufficiently pronounced effect.

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

However, in 2004 there were revolutionary changes in the field of lipid-lowering therapy. Based on the results of the latest HPS and PROVE IT studies, in a specially published supplement to the generally accepted recommendations of NCEP ATP III in a group of patients at high risk ( diabetes, metabolic syndrome, smokers, who have had acute coronary syndrome) a new target level for lowering 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. Simvastatin, pravastatin and atorvastatin have the greatest evidence base for the effectiveness and safety of treatment.

ACE inhibitors. The recently published European Society of Cardiology Expert Consensus on the use of ACE inhibitors in CVD (2004) states that the use of this group medicines required for left ventricular dysfunction and/or heart failure. In coronary artery disease without heart failure and left ventricular dysfunction, efficacy in reducing mortality has been proven only for tissue ACE inhibitors ramipril and perindopril. Only for these drugs, the theoretical background and data from experimental studies have been confirmed in large randomized controlled trials of HOPE and EUROPA. The results of the studies are so convincing that it was on their basis that a new indication for the appointment of ACE inhibitors was added - secondary prevention. cardiovascular diseases without heart failure or left ventricular dysfunction (ESC, 2004). And in October 2004, the American College of Physicians (ACP), based on these studies, recommended the use of ACE inhibitors for all patients with stable angina, 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 classes of drugs used. The risk of death is lowest when all four classes of drugs are used concomitantly. With such complex treatment the highest possible degree of reduction in the risk of coronary artery disease complications and death is achieved.

Drug treatment of angina pectoris, aimed at eliminating symptoms. In the treatment of angina pectoris, three classes of antianginal drugs are used: β-blockers, long-acting Ca antagonists and nitrates, long-acting and short-acting (for stopping an angina attack). All these classes of drugs have proven efficacy in reducing the incidence of angina pectoris, both in monotherapy and in combination treatment. The choice of drug, however, remains a difficult task due to the fact that no one class has shown its convincing superiority over the other, while the individual patient's response may be different.

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

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

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

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

Other drugs of this class are not used in practical medicine due to complete inefficiency (preparations of depo-nitroglycerin) or because of low efficiency (isosorbide dinitrate). The continuous use of transdermal drugs is limited due to the development of tolerance to their hemodynamic and antianginal effects.

Ca antagonists. There is a decrease in the value of this class of antianginal drugs. Initially, caution in relation to them in the treatment of coronary artery disease was associated with the use of short-acting drugs in the form of monotherapy, as they increase the incidence of coronary complications and mortality.

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

The authors of this commentary also note that if it is proven that long-acting dihydropyridines are as safe as placebo, there is no data that would allow us to state how much more 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 β-blockers, aspirin, nitrates and statins (ACTION, 2004).

Therefore, at present, the place of non-dihydropyridine Ca antagonists in the treatment of angina pectoris is the replacement of β-blockers in the presence of contraindications to their appointment or the occurrence of side effects during their use, dihydropyridine - the second drug in case of ineffectiveness of monotherapy with β-blockers.

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

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

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

1. Has the level of physical activity decreased since the last visit?
2. Has angina increased in frequency or severity? If this occurs, or if the patient has reduced their level of physical activity so as not to provoke angina, treatment should be in accordance with the principles for managing unstable angina.
3. How does the patient tolerate the treatment?
4. Is there progress in addressing risk factors (particularly hypertension, diabetes, and hyperlipidemia)?
5. Has the patient developed a new disease in the past period and does the comorbidity affect angina pectoris?

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

1. Repeat ECG when using drugs that can affect conduction when the nature of the pain syndrome changes, palpitations or interruptions in the activity of the heart.
2. X-ray in a patient with the appearance of a heart failure clinic or its aggravation.
3. Echocardiography with the determination of EF and segmental contractility in the event of a heart failure clinic or its aggravation.
4. ECG - stress testing in patients with changed pain syndrome in the absence of ECG anomalies (WPW syndrome, ST depression more than 1 mm at rest or complete blockade LNPG).
5. In the presence of ECG anomalies specified in paragraph 4, radionuclide testing. With a history of revascularization, as well as questionable ECG testing data.
6. Coronary angiography in patients with angina FC 3 despite the maximum drug therapy.

Choice of drugs

3 - selection of a specific drug

Principles of drug selection for the treatment of chronic heart failure. Peculiarities of CHF pharmacotherapy in patients with heart defects.

1. ACE inhibitor (enalapril) or ARB (losartan)

2. V-AB (metoprolol)

3. Diuretics (furosemide)

4. Cardiac glycosides (digoxin)

5. Aldosterone antagonists (spironolactone)

With I FC - 1.2

With II FC - 1-4

With III and IV FC - 1-6

With heart defects - BMKK (nifedipine)

Violations heart rate and conductivity. Classification of antiarrhythmic drugs and indications for the use of antiarrhythmic drugs.

(still in question 100, 57-60)

Classification:

Class I - sodium channel blockers (A-quinidine, B-lidocaine, C-propafenone)

Class II - B-AB (propranolol)

Class III - potassium channel blockers (amiodarone)

Class IV - slow calcium channel blockers (verapamil)

4. Tachyarrhythmias. Principles for choosing an antiarrhythmic drug.

(still in question 100, 57-60)

Tachyarrhythmias:

1. Supraventricular

atrial

atrioventricular

2. Ventricular

The use of diuretics in the pharmacotherapy of cardiovascular diseases. Classification, pharmacodynamic effects.

(in 101 more questions)

Classification:

1. Osmotic - cause water diuresis (mannitol)

2. Saluretics - increase the release of Na and K (loop - furosemide, thiazide - hydrochlorothiazide)

3. Potassium-sparing - increase the release of Na and block the release of K (spironolactone)

Thiazides are used in hypertension, CHF

Arterial hypertension.

(still in question 102)

ACE inhibitor - enalapril

ARB - lozatan

B-AB - bisoprolol

BMCC - amlodipine

Thiazide diuretics - hydrochlorothiazide, indapamide

In the treatment of hypertension, it is necessary to maintain the target level - below 140/90.

Begin treatment with the appointment of one drug in the minimum daily dose. In patients with grades II and III, treatment begins with a combination of 2 drugs. The goal of each stage is to reduce blood pressure by 10-15 mm Hg. If blood pressure does not decrease, gradually increase doses or add new drugs.

Combined antihypertensive therapy.

Advantages:

Strengthening the hypotensive effect

Reducing the incidence of side effects due to both lower doses of combined drugs and mutual neutralization of these effects.

BMKK and diuretics are combined with all the others.

Hypertensive crisis

Vasodilators (enalapril, nitroglycerin, sodium nitroprusside)

Diuretics

Antiadrenergics (phentolamine)

Antipsychotics (droperidol)

Ganglioblockers (Pentamine)

Complications of GC:

Hypertensive encephalopathy - sodium nitroprusside, enalapril, B-AB.

ONMK - enalapril, B-AB.

ACS, acute LV failure, dissecting aortic aneurysm - enalapril, B-AB, nitroglycerin

Pheochromocytoma - phentolamine

Stable angina:

Relief of seizures:

Nitroglycerine

V-AB or BMKK

Forecast improvement:

Aspirin 75mg/day

Non-drug treatment:

Smoking cessation, alcohol cessation, elimination of fatty foods, treatment of concomitant diseases (AH, DM)

Myocardial infarction:

Pain relief - morphine

Antithrombotic drugs - antiplatelet agents (aspirin), anticoagulants (heparin)

Anti-ischemic drugs - V-AB or BMKK, nitrates.

Plaque stabilizing drugs – ACE inhibitors, statins

Pneumonia

Outpatient:

Penicillins (amoxicillin)

Macrolides (azithromycin)

Cephalosporins (ceftriaxone)

Fluoroquinolones (ciprofloxacin)

Intrahospital:

Stage 1 - until the pathogen is detected (1-2 days) - antibiotics acting on gram-trial bacteria - cephalosporins of the 3rd generation (ceftriaxone)

Stage 2 - after the detection of the pathogen (3-4 days) - penicillins (amoxiclav), fluoroquinolones (moxifloxacin), clindamycin

Stage 3 - from day 7 - oral drugs - 3rd generation cephalosporins, aminoglycosides (gentamicin), fluoroquinolones.

COPD

M - anticholinergics (ipratropium bromide)

B2 - adrenomimetics (salmeterol, salbutamol)

Theophylline preparations

Inhaled glucocorticosteroids (beclomethasone)

oxygen therapy

Antibacterial therapy (amoxicillin + clavunalic acid)

Gastritis. Ulcer disease.

(in 121 more questions)

Antihelicobacter therapy (7-14 days):

proton pump inhibitor ( omeprazole 20 mg/2 times a day) + 2 antibiotics ( amoxicillin 1g/2 times a day + clarithromycin 500 mg / 2 times a day).

omeprazole + bismuth subsalicylate(120 mg/4 times a day) + tetracycline(500mg/4 times daily)+ metronidazole(500 mg/3 times a day)

Antacids (sodium bicarbonate), blockers of H2-histamine receptors (ranitide).

Pharmacotherapy of pancreatitis.

Pain relief - antispasmodics (baralgin)

Replacement therapy (lipase) - mezim, festal

If necessary, insulin therapy

From therapy:

Reduced acid production (hunger, omeprazole 20 mg 2 times a day)

Direct suppressive effect on pancreatic secretion (somatostatin)

Termination of the process of autoactivation of enzymes (fluorouracil)

Motor function correction: prokinetics (dommperidone 10 mg 3 times a day)

Relief of water and electrolyte disorders (rheopolyglucin)

Pharmacotherapy of hypothyroidism.

Hypothyroidism - deficiency of thyroid hormones

Weakness, drowsiness, weight gain, bradycardia, TSH elevated

Preparations thyroid gland- levothyroxine sodium. Start with low doses (25 mcg) and gradually increase to effective (100-200 mcg)

The effectiveness of treatment is evidenced by the disappearance of symptoms and the normalization of the concentration of TSH in the blood.

Digoxin

(back in 109)

Effects:

Increase in the force of contractions of the heart, decrease in heart rate, worsening of conduction

Indications:

Acute and chronic heart failure, atrial fibrillation and flutter.

Dose selection:

In the treatment of cardiac glycosides, two periods are distinguished: the period of saturation and the period of maintenance therapy. Each patient has his own individual loading dose (2 ng/ml). The therapeutic effect is preserved if the blood contains at least 80% of the IND, and its excess by 50% leads to the development of intoxication. Saturation can be done at a fast (within a day), medium (3-4 days) and slow (5-7 days) pace. With an average rate of saturation on the first day, about half is administered, and with a slow rate, about a quarter of the average saturating dose. A fast rate of satiety may be necessary in patients with severe acute onset heart failure.

Factors affecting pharmacokinetics and pharmacodynamics:

A decrease in glomerular filtration slows down the excretion of digoxin, as a result, its concentration in the blood exceeds the therapeutic one.

In hyperthyroidism, the concentration of glycosides decreases as a result of their biotransformation.

In the elderly, sensitivity to glycosides increases.

Glycoside toxicity:

Cardiac manifestations: tachycardia, bradycardia, arrhythmias

Extracardiac: nausea, vomiting, diarrhea, blurred vision, fatigue, headache, dizziness,

With the development of glycoside intoxication, glycosides are canceled, antidotes (unithiol, atropine) are administered, and symptomatic therapy is carried out. As antiarrhythmic drugs - drugs of class IB (lidocaine), with bradycardia, AV blockade - M-HB.

Interaction with other drugs:

Interaction with ACE inhibitors in CHF increases the effectiveness of each drug

The inotropic effect of glycosides is increased by B2-agonists

Arrhythmogenic effect is eliminated by antiarrhythmics IB (lidocaine)

Drugs that reduce intestinal motility (M-anticholinergics, antispasmodics) improve the absorption of glycosides, and those that increase peristalsis (M-cholinomimetics) reduce absorption.

Tuberculosis

Principles of treatment:

Long-term maintenance therapy

Prescribing at least 2 first-line drugs

Ensuring regular medication intake

Neglect of these principles leads to the development of multidrug-resistant forms of tuberculosis.

For the treatment of newly diagnosed tuberculosis, drugs of the first line are used - isoniazid and rifampicin, and the combination of other drugs of this series with them makes it possible to achieve a cure for most patients. There are various combined drugs, they include various combinations of drugs of the first line.

For the treatment of multidrug-resistant tuberculosis, drugs of the second line are used.

Classification:

First line drugs: isoniazid, rifampicin, streptomycin, pyrazinamide, ethambutol

Second-line drugs: ethionamide, kanamycin

Isothiazid: hepatotoxicity, damage to the nervous system (neuritis, atrophy of the optic nerve, muscle twitches, convulsions), during pregnancy - a delay in the psychomotor development of the child.

Rifampicin: Dyspeptic disorders, hepatotoxicity (increased ALT, AST, bilirubin). allergic reactions(rash, angioedema), influenza-like syndrome (headache, fever, bone pain), thrombocytopenic purpura.

Criteria for evaluating efficacy and safety antibiotic therapy. Examples.

Efficiency:

Normalization of t, disappearance of symptoms. Decrease in the number of leukocytes, ESR, CRP.

Security:

To assess the safety of antibiotics, it is necessary to detect possible ADRs clinically and in the laboratory. For example, when taking drugs with a nephrotoxic effect, monitor kidney function (blood creatinine).

Routes of drug administration. Factors affecting the choice of routes of administration. Examples.

I. Enteral administration

Advantages in simplicity and convenience. ABs are prescribed before meals, because the absorption of many of them depends on food. NSAIDs after eating, because they irritate the gastric mucosa. The disadvantages are that the absorption of many drugs depends on the state of the gastrointestinal tract, some drugs (insulin) are destroyed in the stomach, some drugs (NSAIDs) adversely affect the stomach and intestines.

2. Sublingual

The action of the drug begins quickly. The rate of absorption does not depend on food intake. An example is nitroglycerin.

3. Rectal

Used for drugs with a high metabolism. Assign drugs that irritate the gastric mucosa (NSAIDs).

II. parenteral administration

1. Intravascular (usually IV)

Provides fast creation of high concentration. In this way, it is possible to prescribe drugs that break down in the gastrointestinal tract (insulin), irritate the gastrointestinal tract or are not absorbed in it (aminoglycosides). The disadvantages include various technical difficulties, the risk of developing infections at the injection site.

2. Intramuscular administration

Absorption into the blood takes 10-30 minutes. No fundamental advantage

3. Subcutaneous

You can enter insulin or heparin.

4. Inhalation

Preparations for the treatment of lungs and bronchi

5. Endotracheal

in intensive care practice.

Absorption of drugs: definition, mechanisms. Factors affecting absorption during parenteral administration of drugs. Examples.

Absorption (suction) - the process of receipt of drugs from the injection site into the circulatory and / or lymphatic system. Drugs are able to overcome cell membranes without violating their integrity using a number of mechanisms: passive diffusion, active transport, filtration, pinocytosis.

Solubility, chemical structure and molecular weight of drugs are important for the absorption of drugs in the body. Solubility in water increases in the presence of an alcohol group in the drug. The rate of absorption of drugs after the / m injection also depends on the intensity of blood circulation at the injection site.

Factors affecting the absorption of drugs when taken orally. Examples.

Gastrointestinal motility. pH of stomach contents.

Eating. For example, the absorption of penicillins after a meal slows down, while the absorption of metoprolol, on the contrary, accelerates.

Dosage form. Solutions, suspensions, capsules, simple tablets are better absorbed.

distribution of drugs in the body. Factors affecting distribution. Examples.

Solubility in lipids

Degree of binding to plasma proteins

Intensity of regional blood flow

The presence of biological barriers (hematoenphalic barrier, histohematic, plasma membranes, capillary wall)

Binding of drugs to blood proteins. Factors affecting binding. Examples.

Proteins: albumins, lipoproetins, acidic a-glycoprotein, y-globulins.

Elderly age, high-fat meals, kidney and liver disease.

Metabolism of drugs. Biotransformation reactions. Factors affecting metabolism. Examples.

The biological role of this process is to create a substrate suitable for further utilization or to accelerate excretion from the body.

Phase I metabolism - a change in the structure of a drug through its oxidation, reduction or hydrolysis, etc. Aimed at achieving drug activity

Phase II metabolism - binding of drug molecules. For example, methylation, acetylation. Directed to the removal of drugs.

Biotransformation is affected by: age, gender, diet, concomitant diseases, environmental factors. The most significant organs for biotransformation are the liver and intestines.

Presystemic elimination of drugs. Examples, value for optimizing pharmacotherapy.

These are the processes of biotransformation before the entry of drugs into the systemic circulation. If, as a result of active first pass metabolism, substances with less pharmacological activity than the original drug are formed, then parenteral administration is preferable.

An example of a drug with a high first pass metabolism is nitroglycerin, which is active when taken sublingually and intravenously, but completely loses its effect when taken orally.

Excretion of drugs from the body: the main ways, mechanisms. Factors affecting the excretion of drugs by the kidneys. Examples, value for optimizing pharmacotherapy.

Most drugs are excreted from the body by the kidneys, to a lesser extent - by the lungs through the sweat glands, salivary glands, with breast milk, liver.

Excretion of drugs occurs through: glomerular filtration, passive reabsorption in the tubules.

Pharmacological effects of drugs. The concept of affinity. Agonists, antagonists, partial agonists of receptors, antagonists with their own activity. Drugs that have a non-specific, specific, selective effect. Examples.

1. Physiological effects - changes in blood pressure, heart rate.

2. Biochemical - increased levels of enzymes in the blood

Affinity - the strength of the binding of a substance to receptors.

Internal activity - the ability of a substance after their interaction with receptors to cause physiological or biochemical reactions corresponding to the functional significance of these receptors.

Agonists are substances that have both affinity and internal activity. Drugs with a pronounced intrinsic activity are full agonists, and less pronounced activity are partial agonists.

Antagonists are substances that have affinity and do not have internal activity.

Drugs that provide nonspecific action cause a wide range of pharmacological effects. This group includes, for example, vitamins, glucose, amino acids. They have a wide range of uses.

If a drug acts as an agonist or antagonist on the receptors of certain systems, then its action is called specific.

Selectivity is manifested in the event that drugs change the activity of one of the components of the systems. For example, propranolol blocks all B-adrenergic receptors, while atenolol blocks only B1.

157. Minimum therapeutic concentration, therapeutic range, therapeutic breadth, average therapeutic concentration, therapeutic index of the drug: definitions, significance for optimizing pharmacotherapy.

The minimum therapeutic concentration is the concentration of the drug in the blood, causing an effect equal to 50% of the maximum.

Therapeutic range - the range of concentrations from the minimum therapeutic to causing the appearance of the first signs of side effects.

Therapeutic latitude - ratio upper bound therapeutic range to lower

The average therapeutic concentration is an intermediate concentration of the therapeutic range.

Therapeutic index is an indicator reflecting the ratio of the average lethal dose to the average therapeutic.

Types of pharmacotherapy. Purpose and objectives of rational pharmacotherapy. Stages of rational pharmacotherapy.

1. Etiotropic - elimination of the cause of the disease (antibiotics for infectious diseases)

2. Pathogenetic - impact on the mechanism of disease development (ACE inhibitors in hypertension)

3. Symptomatic - elimination of individual symptoms or syndromes (antipyretic for influenza)

4. Substitution - in case of insufficiency of natural biologically active substances (insulin in diabetes)

5. Preventive - prevention of the development of an acute process or exacerbation of a chronic one (vaccines, serums)

Determination of indications for pharmacotherapy

Choice of drugs

The choice of routes and methods of administration

Determination of the individual dose

1 - diagnosis, determination of the severity of the condition

2 - choice of pharmacological group of drugs

3 - selection of a specific drug

4 - change in pharmacotherapy in case of stabilization of the condition or its ineffectiveness

5 - conducting pharmacotherapy during the period of convalescence (with acute diseases) or remission (for chronic).

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

The response to pharmacotherapy depends both on the characteristics of the individual patient and on his behavior, habits (using certain foods and nutritional supplements, following the prescribed dosing regimen), the presence of renal or hepatic insufficiency, other concomitant diseases, taking other drugs. Errors in prescribing medicines (selecting the wrong drug, misreading the prescription, taking the wrong drug) also affect the effectiveness of treatment.

Adherence to prescribed pharmacotherapy

Adherence (compliance) is a measure of how strictly the patient follows the prescribed treatment plan. In the case of drug therapy, adherence to the prescribed regimen implies the timely receipt of the drug and its use in strict accordance with the prescribed dose, frequency of administration and duration of treatment. Patients should be reminded that in case of discontinuation or deviation from the prescribed dosing regimen of the drug, it is necessary to inform the attending physician about this, which rarely happens in practice.

Only about half of the patients take their medicines as prescribed by their doctor. The most common reasons for non-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;
• the cost of treatment.

There are other reasons as well. Children are less likely to adhere to the prescribed treatment regimen. The lowest compliance is observed in chronic diseases requiring complex long-term treatment. Parents may not fully understand instructions for use of drugs and after 15 minutes forget half the information received from the doctor.

Elderly patients adhere to the therapy regimen to the same extent as other adult patients. However, factors that reduce compliance (eg, financial difficulties, use of multiple drugs or drugs that require multiple doses per day) are more common among older patients. Cognitive impairment can further reduce compliance. Sometimes the prescribing physician has to be creative in choosing a drug, prescribing the most easy-to-use alternative available. For example, in hypertensive patients who have difficulty taking oral medications, clonidine may be given as a transdermal therapeutic system, which must be replaced weekly by a nurse or family member.

The most obvious result of non-compliance with the prescribed regimen of therapy is the inability to alleviate 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 placements, up to 10% of hospital admissions, many doctor visits, diagnostic tests, and many unnecessary treatments. In some cases, reduced compliance can lead to an increase in the severity of the disease. For example, skipping a dose or early cancellation of antibacterial or antiviral therapy contributes to the growth of resistance of pathogens.

Pharmacists and pharmacy pharmacists and nurses can help identify and resolve non-compliance problems. For example, a pharmacy employee may note that the patient does not come to re-fill his prescribed drug, or does it prematurely. By discussing physician prescriptions with the patient, the pharmacist or nurse can identify and help resolve 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.

Mistakes in prescribing medications

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

Their main reasons are:

• Incorrect choice of drug, administration of an inadequate dose, incorrect dosing regimen and / or duration of therapy.
• An erroneous reading of a prescription by a pharmacy employee, as a result of which the wrong drug or its dosage is dispensed.
• Erroneous reading of the packaging by a pharmacy employee, as a result of which the wrong drug or its dosage is dispensed.
• Incorrect instructions to the patient.
• Incorrect administration of a drug by a healthcare worker or patient.
• Improper storage of the drug by a pharmacy employee or a patient, which leads to a decrease in its activity.
• The use of drugs with an expired shelf life, which leads to a decrease in their activity.
• Improper drug intake by the patient.

Errors in prescribing drugs are very common, especially in certain categories of patients. The risk group includes the elderly, women of childbearing age and children. Drug interactions are especially common in patients receiving multiple drugs. To reduce the risk, it is necessary to know all the drugs the patient is taking (including those prescribed by other doctors and available without a prescription) and keep their list up to date. Patients should be encouraged to keep a complete list of their medications so that they can be shared with their doctor or other healthcare professional if necessary. The recipe should be written as clearly as possible.

The names of some drugs are similar, which can cause confusion if they are spelled illegibly. Avoiding errors helps deciphering some of the traditional designations, which can be misread. For example, "1 r/d" is easily confused with "4 r/d", so it is preferable to write "once a day". Using recipes printed on a printer helps to avoid problems associated with illegible handwriting or incorrect abbreviations.

Errors in prescribing drugs are also possible in medical institutions. In particular, the drug may be given to the wrong patient, at the wrong time, or the wrong route of administration may be erroneously prescribed. Some drugs must be given slowly intravenously; some - cannot be entered in parallel. If such errors are detected, it is necessary to immediately inform the doctor and get advice from the pharmacist. Electronic dispensing systems reduce the likelihood of such errors.

Drugs should be stored in such a way as to ensure that their potency is maintained. Pharmacies that distribute drugs by mail must also comply with the necessary transport regulations. Often drugs are stored incorrectly by patients, in which case it is more likely that they will lose their effectiveness long before the expiration date. The packaging should clearly indicate whether the drug should be stored in a refrigerator or in a cool place, protecting from exposure. high temperatures or sunlight, or observing special storage conditions. On the other hand, unnecessary precautions reduce the likelihood of compliance with the prescribed therapy regimen and lead to unnecessary waste of the patient's time. For example, unopened insulin should be kept refrigerated; however, an open vial can be stored for a long time outside the refrigerator, in a place that excludes exposure to excessively high temperatures or direct sunlight.

The use of expired medicines 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 be informed about what dose of the drug should be taken and why this particular drug was prescribed. It is desirable that this information be kept in writing by the patient. You should also be advised to consult a pharmacist about the use of the drug. Packaging should be convenient, but safe. If there is no likelihood of children having access to medicines and if the patient has difficulty opening the container with the drug, plain packaging without child protection mechanisms should be used.

Drug Interactions

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

Drug interactions can lead to an increase or decrease in the effect of one or more drugs in the combination. Clinically significant interactions are often predictable and usually undesirable because may lead to the manifestation of side effects, or the absence of a therapeutic effect. Less commonly, clinicians may use predictable drug interactions to achieve the desired 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 at the same time, their effects may be summed up. For example, when a patient takes one benzodiazepine as a tranquilizer and another as a sleeping pill at night, their cumulative effect can lead to manifestations of toxicity.

Drug interactions are subdivided into:

• for pharmacodynamics,
• pharmacokinetic.

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

When interacting pharmacokinetically, one of the drugs in the combination usually alters the absorption, distribution, protein binding, metabolism, or elimination of the other. Accordingly, the amount and duration of the impact of the first drug on the receptor changes. Pharmacokinetic interaction changes the severity and duration of the effect, but not its type. Often, it can be predicted based on the characteristics individual drugs, or to identify in the process of monitoring their concentration or clinical symptoms.

Minimization of drug-drug interactions. The attending physician should be aware of all the medicines that the patient is taking, incl. prescribed by other specialists, over-the-counter, as well as nutritional supplements. It is advisable to ask the patient about the nature of food 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 drugs taken, as they usually include a range of potential drug interactions. In order to avoid manifestations of toxicity due to unpredictable drug interactions, drugs with a wider therapeutic window should be used.

Patients should be observed for the development of adverse reactions, especially after changes in the treatment regimen have been made; some types of interactions (for example, as a result of enzyme induction) may appear after a week or later. Drug interactions should be considered as possible cause any unforeseen complications. With the development of an unexpected clinical reaction, the doctor may need to determine the concentration of individual drugs taken in the blood serum. 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 that the patient receives.

Pharmacogenetics

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

The activity of drug-metabolizing enzymes often varies widely in healthy individuals. As a result, the rate of elimination of a particular drug can differ by dozens of times. Most of these differences are due to genetic factors and aging.

Genetically determined changes in drug metabolism (for example, due to 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 need higher doses or more frequent dosing to achieve therapeutic blood levels. At the same time, patients who slowly metabolize certain drugs, in order to avoid intoxication, may need to prescribe 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 bowel disease who require azathioprine, thiopurine methyltransferase (TPMT) genotyping is performed to determine the optimal starting dose of the drug. Most genetic differences cannot be predicted prior to prescribing, 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, the interaction of environmental factors and the patient's body is possible, which leads to a change in the response to drug therapy.

placebo

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

The term placebo (Latin for “I will please you”) originally referred to inactive, harmless substances that were given to patients in order to improve their well-being under the influence of the power of suggestion. Later, sham interventions (for example, sham electrical stimulation, simulated surgical procedures) began to be classified as placebo. The term is sometimes used to refer to active drugs given solely as a placebo for diseases for which they are in fact ineffective (for example, an antibiotic for patients with viral infection). Manifestations of the placebo effect are more often subjective (eg, headache, nausea) than objective (speed of wound healing, degree of burn infection).

effects. Although placebos are physiologically inactive, they can have a real effect - positive or negative. These effects are usually associated with the expectation that the drug will work; The anticipation of adverse reactions is sometimes referred to as the nocebo effect. The placebo effect usually occurs with subjective responses (eg, pain, nausea) rather than objective responses (eg, rate of ulcer healing, burn wound infection rate).

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 sure that he is receiving the active substance than when he knows that he may be receiving a placebo);
• placebo type (substances for intravenous administration have a greater effect than those taken orally).

The placebo effect is not observed in all patients, in addition, it is impossible to predict in advance who will experience it. The relationship between personality traits and placebo response has been repeatedly discussed, but in reality is not fully established. However, patients who are highly 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 studies. In many clinical studies, the effect of active treatment is compared with placebo. The estimated placebo effect must then be subtracted from the total observed effect to determine the true treatment effect. In other words, it is necessary to evaluate clinical and statistically significant differences. 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 given when the doctor decides that the patient's illness is mild and does not require active medication, or when effective treatment absent in principle (for example, in the case of non-specific malaise, fatigue). Often this is justified by the fact that it satisfies the desire of the patient to receive treatment without exposing him to the risk of adverse reactions and, in some cases, making him feel better (due to the placebo effect or spontaneous improvement).

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

At the same time, when a patient is given a placebo in actual clinical practice, they are not told they are receiving inactive treatment. In this case, the ethics of misleading the patient becomes moot. Some clinicians consider this approach inherently unethical and, if known, damaging to the doctor-patient relationship. Others argue that it is far more unethical to not give a patient any treatment, thereby depriving the patient of the opportunity to feel better. Prescription to the patient pharmacologically active drug solely as a placebo can also be considered contrary to the principles of bioethics, since in this case the patient is exposed to the possible risk of real side effects (as opposed to the nocebo effect).

New drug research

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

In early preclinical studies, potentially active compounds are studied in animals to evaluate the desired effect and toxicity. Substances that have shown their effectiveness and safety become candidates for further study in humans. In the US, a protocol containing a description clinical trial, must be approved by the Institutional Review Board and the U.S. Food and Drug Administration (FDA), who then grant approval for investigation of the new drug. From this moment begins the period of validity of the patent for the drug, usually giving the owner exclusive rights for the next 20 years; however, a drug cannot be placed on the market without FDA approval.

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

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

Phase 3 studies are evaluating the effect of the drug in larger (100 to several thousand people) and heterogeneous groups of patients to confirm the possibility of clinical use of the study drug. During this phase, the drug is also compared with existing standard treatment regimens and / or placebo. Clinicians and many hospitals 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 detected in studies of the 1st and 2nd phases.

When sufficient data are collected for the registration of the medicinal product, the materials are submitted to the controlling organization, which gives permission to release it to the market. Since early stage drug development often takes about 10 years before registration.

Phase 4 studies are conducted after the drug receives registration and goes on sale. Such studies are usually continuous and involve large patient populations. Often, such studies include special subgroups of patients (eg, pregnant women, children, elderly patients). Phase 4 studies also suggest regular reports of adverse events that have developed with the use of 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.

Topic 1. Fundamentals 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.

Tasks and significance of pharmacotherapy in medicine and pharmacy.

Routes of introduction of drugs into the body.

Types of action of drugs

HP compatibility.

Features of pharmacotherapy in children and the elderly.

Pharmacotherapy in elderly and senile patients.

Features of pharmacotherapy in pregnant women and nursing mothers.

Pharmacotherapy - a branch of pharmacology that studies the therapy of a patient 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 antimicrobials for infectious diseases or antidotes (antidotes) for poisoning with toxic substances. This type of therapy is the most effective.

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

Symptomatic therapy It 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. Drugs that eliminate individual manifestations of the disease are called symptomatic drugs. Their therapeutic effect is based only on the weakening of some symptom of the disease.

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

Replacement therapy is used in case of insufficiency in the patient's body of biologically active substances (hormones, enzymes, vitamins, etc.), the introduction of which, without eliminating the causes of the disease, ensures a normal life for a person for many years (type I diabetes mellitus, hypothyroidism, anemia associated with iron deficiency , lack of vitamin B,2 and folic acid, chronic adrenal insufficiency, etc.).

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

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

Pharmacotherapy strategy It comes down to eliminating or reducing the action of the causes that cause diseases, eliminating or suppressing the mechanisms of the development of the disease, on the one hand, and also stimulating the 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 enhance the body's defense mechanisms, so the doctor sometimes justifiably seeks to simultaneously prescribe several drugs (polypharmacy).

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

In carrying out rational individual pharmacotherapy based on knowledge of pharmacokinetics, metabolism of drugs, pharmacogenetics and pharmacodynamics, a pharmacist provides essential 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 of new pharmacological agents;

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

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

4) information support and advisory assistance to medical workers.

Resolves issues such as:

1) the choice of a medicinal product for the treatment of a particular patient;

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

5) prevention and elimination of adverse drug reactions.

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

1) the choice of drugs for the treatment of a particular patient;

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

3) determination of routes of drug administration;

4) monitoring the effect of the medicinal product;

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

Pharmacology is a biomedical 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 - doctrine, word. Thus, the literal translation: pharmacology - the science of medicines, pharmacology. Modern pharmacology 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, the technology of manufacturing medicines at the factory and in the pharmacy. 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 drug action is considered as an effect 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 a convenient for use form of release of the drug (solid, liquid, soft, extraction and maximally purified).

An important information characteristic of medicines is their international non-proprietary names (INN). They, identifying the active pharmaceutical substance (about 8000 in the world), provide communication and information exchange between healthcare 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 multicomponent preparations produced in a specific dose and dosage form. Trade names are the property of the manufacturer. In Russia

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

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

each stage life cycle medicinal product complies with the standard of "good practice" (Good practice) or code of practice. Standards guarantee the effectiveness, safety and pharmaceutical aspects of the quality of 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 cell culture and their organelles. These studies should provide evidence and reliability of data while respecting the principles of humane treatment of laboratory animals. The following experimental methods are used:

screening to screen - sift) - standard methods assessment of the activity of chemical compounds in comparison with the action 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, methods of molecular biology;

study of pharmacokinetics;

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 effect 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, the development of methods for the effective and safe use of drugs, the elimination of undesirable consequences of their interaction, the conduct of pharmacokinetic studies, the organization of an information service.

table1. Good Pharmaceutical Practice Standards

Clinical trials of new drugs of I-IV phases (Table 2) are carried out in comparison with the action of reference drugs of this pharmacological group or placebo. placebo (lat. placebo - like) is a dosage form that does not contain a drug, has the same appearance, smell, taste, like a real drug. The placebo effect is especially important in 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, initial background treatment. Groups are formed by random distribution of patients (randomization).

Table 2. Phases of clinical trials

Clinical trials use open, single-blind, and double-blind methods. At "simple blind" The method does not tell the patient whether he or she has taken the test drug, the reference drug, or the placebo. This is known to the doctor and the customer of the study. At "double blind" method, neither the patient nor the attending physician has information. Only the customer of the study is informed about how the clinical experiment is carried out. Apply clinical, instrumental, laboratory and morphological methods.

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

The creation 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 medicine. The duration of collecting data on the created drug reaches 8 - 12 years.

In addition to the beneficial therapeutic effect, many drugs can cause adverse reactions, in some cases leading to severe complications and even death.

Adverse reactions and complications are possible when taking any medication.

Modern medicine has made great strides 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 drugs has increased dramatically. Their frequency in outpatient treatment reaches 10-20%, and 0.5-5% of patients need 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.

There are the following types of side effects and complications of pharmacotherapy:

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

2) toxic complications, regardless of the dose;

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

4) allergic reactions;

5) withdrawal syndrome that occurs when you stop taking the 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.

An overdose of drugs can be absolute (too high a dose taken) and relative (the dose is therapeutic, and the concentration in the blood and cells is too high, due to the peculiarities of the pharmacokinetics of the drug in this patient). With an overdose, there is a significant increase in the main and toxic effects of drugs. For example, with an overdose of vasodilators, collapse occurs, excitatory - convulsions, hypnotics - anesthesia, etc.

Complications, when using the drug in usual therapeutic doses, not associated with an overdose, do not occur in all patients and, as a rule, with prolonged 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 dose, in some cases for some drugs cannot be avoided at all. For example, cytostatics not only inhibit 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 with the use of highly active antibiotics and other antimicrobial agents that cause changes in the normal bacterial microflora (superinfection, dysbacteriosis, candidomycosis).

Side effects of drugs depend on the nature of the underlying disease. Systemic lupus erythematosus is more often accompanied by steroid arterial hypertension.

Allergic reactions are the most common complication of drug therapy. Allergic reactions are caused by the interaction of an antigen with an antibody and are not related to the dose of drugs. There are two types of immunopathological reactions that can be caused by drugs: 1) an 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, chlorpromazine, local anesthetics, sulfanilamide, 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, long-acting drugs should not be prescribed. A careful collection of a family history will help to identify the presence of idiosyncrasy in a patient - a primary intolerance to drugs that is inherited. Idiosyncrasy occurs on iodine preparations, quinine, sulfanilamide, etc.

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

Side effects may 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 mucosa of the gastrointestinal tract and cause nausea, vomiting, and the formation of erosions on the gastric mucosa. Therefore, they should be taken after meals. It's 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 be manifested by 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 a direct effect of drugs on the heart muscle, causing rhythm and conduction disturbances, a decrease or increase in blood pressure, and a violation of myocardial contractility. Hypersensitivity reactions to drugs may be the cause of allergic myocarditis.

Possible disorders of the nervous system (depression, convulsions, extrapyramidal disorders, hearing and vision loss, polyneuropathy, etc.). Nerve cells are highly sensitive to chemicals, so drugs that penetrate the blood-brain barrier can disrupt performance, cause headache, dizziness, lethargy, etc. Thus, with prolonged use of neuroleptics, parkinsonism develops, tranquilizers - gait disturbance (ataxia) and depression, excitatory - insomnia, etc. The impact of drugs sometimes leads to degenerative changes and even death of the nerve fiber and cell. So, 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.) can cause optic neuritis, etc. Some drugs also affect on the organ of vision, causing damage to the optic nerve, cataracts, increased intraocular pressure, retinopathy and conjunctivitis.

The liver is a barrier between the intestinal vessels and the general circulatory system. With enteral administration (especially) and with any other, it is here that most medicinal substances accumulate and undergo biotransformation. In this case, the liver may suffer, especially if the drug is concentrated in hepatocytes and retained for a long time - the basis for the manifestation of hepatotoxicity. Cytostatics, some antibiotics, 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 (halothane, chlorpromazine, chloral hydrate, etc.), arsenic, mercury, some antibiotics (tetracycline, streptomycin) and others have high hepatotoxicity. A liver rich in glycogen and vitamins is more resistant to chemical agents.

The kidneys, as an organ of excretion, concentrate drugs - the basis for the manifestation of nephrotoxicity. Damage to the 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. The nephrotoxic effect is exerted by antibiotics of the aminoglycoside group (streptomycin, gentamicin, neomycin), butadione, sulfa drugs, vasoconstrictors, etc. It is currently believed that a significant part of nephrological disorders is associated with the occurrence of an allergic process. To the formation of stones in urinary tract with prolonged use, calcium preparations, sulfonamides, etc.

Most oral medications affect the lining of the mouth 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, intestines, gastrointestinal bleeding, exacerbation of pancreatitis. All this is the basis for the ulcerogenic effect (the formation of ulcers on the mucous membranes). Ulcerogenicity is possessed by glucocorticoids, non-narcotic analgesics, reserpine, tetracycline, caffeine, etc.

Many drugs cause changes in the blood. One of the most dangerous complications drug therapy is the oppression of hematopoiesis - hematotoxic effect. So, when using antiepileptic drugs, anemia can be observed; chloramphenicol, butadione, amidopyrine, sulfanilamide drugs and others - leukopenia up to agranulocytosis, which is often manifested primarily by ulcerative necrotic lesions of the oral mucosa. Agranulocytosis often develops with the appointment of non-steroidal anti-inflammatory drugs (amidopyrine, indomethacin, butadione), as well as in the treatment of captopril, chloramphenicol, tseporin, furosemide, etc. Hemolytic anemia occurs with the use of 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.

With great care, pharmacotherapy should be carried out 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 metabolism of neurotransmitters, blood coagulation, etc. Teratogenic effects have been found in glucocorticoids, salicylates, tetracyclines, synthetic antidiabetic drugs, anticonvulsants. Currently, all drugs are tested for teratogenic effects before they are introduced into clinical practice.

Much attention is paid to the study of the carcinogenic effect of drugs. This activity is possessed by derivatives of benzene, phenol, tar ointments, cauterizing agents. Sex hormones and other stimulants 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, levomycetin) 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 are sharply exacerbated, which requires the use of antitoxic therapy, antihistamines and glucocorticoids.

Broad-spectrum antibacterial drugs, especially antibiotics, by suppressing the microflora sensitive to them, contribute to the multiplication of resistant microorganisms, dysbacteriosis and superinfection occur. The most common fungus is Candida. Candidiasis usually affects the oral mucosa. To prevent this complication, broad-spectrum antibiotics are combined with antifungal agents (nystatin, levorin, dekamin).

The use of chemotherapeutic 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, erased forms of infectious diseases appear that do not leave lifelong immunity.

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

The phenomena of cumulation, addiction and addiction to drugs. Various phenomena can be associated with the use of medications. So, with repeated or prolonged use of the drug, the phenomenon of cumulation occurs, that is, an increase in its action. Cumulation can be the result of accumulation of a substance (material, chemical cumulation) or accumulation of dysfunctions (physiological, functional cumulation).

With prolonged and frequent use of the drug, addiction can occur - a decrease in the body's response to repeated use of the drug in the same doses. Habituation is manifested in the fact that the required healing effect is not achieved with the introduction of the same dose of the drug, in this case, you should increase the dose of the drug or replace it with another drug of a similar effect.

With the use of drugs that act on the central nervous system(psychotropic drugs), the phenomenon of addiction is associated, which is a drug dependence on a certain drug caused by its systematic use. Addiction is accompanied by a desire to increase the dose of the drug when taken again. This is due to the fact that with the introduction of such drugs, a state of euphoria can 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 cause sleeping pills, narcotic, stimulants and painkillers. Accordingly, according to the name of the drug to which addiction has appeared, drug addictions are called alcoholism, ether addiction, morphinism, cocainism, etc. Drug addicts are seriously ill people who need qualified treatment from a specialist doctor.

The combination of drugs (co-administration) can lead to a mutual enhancement of the effect (synergism) or a mutual weakening of it (antagonism). In cases of drug poisoning, the principles of antagonism must be used.

There are several types of antagonism:

Physico-chemical, based on the absorption of poisons

on the surface of the adsorbent (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 the drugs lose their effect (for example, neutralization of acids with alkalis);

Physiological, based on the administration of drugs,

that have the opposite effect on a given organ or tissue

action (for example, the introduction of stimulants in case of poisoning by 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 medicinal product.

Medicinal raw materials are a source of obtaining a medicinal 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, the waste products of fungi and bacteria, from which hormones, enzymes, antibiotics and others are obtained biologically. active substances. An important role in this is played by genetic engineering, which makes 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 novogalenic preparations are obtained.

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

Novogalenic preparations are water-alcohol extracts from herbal medicinal raw materials, of a high degree of purification with the removal of all ballast substances. Due to this purification, the preparations can be administered parenterally.

A medicinal product (drug) 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” (definition by the WHO scientific team), may contain other substances that ensure its stable form. The terms "drug" and "drug" are used interchangeably. The medicine can have a single-component or complex composition with preventive and therapeutic efficacy. In the Russian Federation, medicinal products are considered drugs that are approved for use by the Ministry of Health in the prescribed manner.

A drug is a drug in a ready-to-use form. This is a dosed medicinal product in an adequate dosage form for individual use and 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 the above provisions, standards are being developed that are approved by state institutions (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 appointment, use, dosing and storage of which, due to their high toxicity, must be done with extreme caution. This list also includes drugs that cause addiction. List B (heroica - potent) includes medicines, the appointment, use, dosage and storage of which must be carried out with caution in connection with possible complications when used without medical supervision. The third group is medicines dispensed from pharmacies without prescriptions.

A prescription is a written instruction from a doctor to a pharmacist about the release or preparation of medicines for a patient with instructions for their use. A prescription is a legal document that only a doctor can write. Prescription - a doctor's request to a pharmacist about dispensing medicines to a patient, indicating the dosage form, dose and method of application. A prescription is a medical, legal and monetary document in the case of free or reduced-price medicines. Prescriptions are written and medicines dispensed according to them are carried out in accordance with the "Rules for Prescriptions", "Rules for the Storage and Dispensing of Poisonous and Poisonous 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 enterprises according to the prescription available in the Pharmacopoeia are called official, and those prepared according to the prescription of a doctor are called manestral.

Means from the list of narcotic substances (capable of causing drug dependence - drug addiction) are prescribed on special forms. Narcotic analgesics, psychostimulants (amphetamine, dexamphetamine and similar compounds). Narcotic antitussives (codeine, codeine phosphate, ethylmorphine hydrochloride). Hypnotics (noxiron, etaminal-sodium, etc.) Anorexigenic drugs (fepranone, depimon, etc.) Cocaine hydrochloride, sombrevin.

A prescription for a narcotic drug must be written in the handwriting 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 by a round seal. This order of prescription is defined for drugs with anabolic activity (anabolic steroids) and intoxicating action - phenobarbital, cyclodol, ephedrine hydrochloride, clonidine (eye drops, ampoules).

Antipsychotics, tranquilizers, antidepressants, preparations containing ethyl alcohol, etc. are prescribed on other forms of prescription forms.

Without a prescription, in the order of manual sale, medicines are dispensed: analgin with amidopyrine 0.25 each (tab.), Avisan, dekamevit, validol, valerian preparations, Zelenin drops, Vishnevsky ointment, nitroglycerin, etc. It is forbidden to write prescriptions for ether for anesthesia to outpatients , chloroethyl, fentanyl, etc.

Recipes consisting of one medicinal substance are called simple, those of two or more substances are called complex. In complex prescriptions, the following order of recording medicines is used: 1) the main medicine; 2) adjuvants (enhancing 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 (preparations that give the drug a certain consistency).

Doses of drugs. For the correct action of drugs, they must be used in an adequate dose. A dose is the amount of a drug that is injected into the body and has a certain effect on it. The strength of the drug is determined by the dose and the order of its administration.

Dose - the amount of a medicinal substance introduced into the body, and is expressed in mass or volume units of the decimal system and is indicated by Arabic numerals. The number of whole grams is separated by a comma. Per unit of weight in the recipe, 1 g is taken - 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, 1 tsp. - 5 g; in 1 g of water - 20 drops; in 1 g of alcohol - 47-65 drops.

According to the mode of action, the dose can be minimal, therapeutic, toxic and lethal.

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

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

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

Minimum lethal (lethal) dose is the amount of a drug that can be lethal.

According to the number of applications per day, the dose can be single (single) and daily.

There are also:

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

Varying doses, difficult to correct. Adequate dose selection is difficult, since the final therapeutic result is difficult to quantify, for example, a state of depression or anxiety, or the effect develops slowly, for example, with thyrotoxicosis or epilepsy, or varies depending on the pathological process (during treatment with corticosteroids).

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

The maximum tolerated dose. Drugs that do not allow to obtain an ideal therapeutic effect due to adverse reactions (anticancer, antibacterial) are used at the maximum tolerated doses, that is, 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 in inflammatory and immunological diseases, for example, in bronchial asthma, rheumatoid arthritis. The dose that causes symptomatic improvement of the condition may be so high that severe adverse reactions are unavoidable. The patient receives a dose that relieves 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, which ensures 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 assimilation 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. The use of a sufficient amount of vitamins helps to strengthen the body, increase its efficiency and resistance to harmful environmental influences.

Lack or absence of vitamins leads to a weakening of the body and the development of characteristic diseases - hypo - and beriberi, in which metabolism and most of the body's functions are disturbed. Hypervitaminosis is an excess intake of vitamins in 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, especially C and P, drops in them. At the same time, people experience weakness, increased fatigue, decreased efficiency and reduced body resistance to infections.

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

For normal cellular metabolism and tissue trophism

For energy transformation

For plastic exchange

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

To ensure the immunological reactivity of the body

For the normal functioning of all organs and tissues.

Pharmacotherapy is inextricably linked with toxicology.

WAYS OF INTRODUCING DRUGS INTO THE ORGANISM

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

Enteral routes of administration