When is the best time to take medications? The importance of circadian rhythms for the manifestation of the action of drugs Sudphanilamides and antibiotics - time of administration

Chronopharmacology- a new direction in pharmacology that studies the interaction of medicinal substances with body systems depending on biorhythms, their physiological and pathological activity. Knowledge of chronopharmacology is necessary to determine the time of day and seasons of the year when the drug will have the best pharmacotherapeutic effect.

Knowledge of the daily, seasonal and other biorhythms of a given person allows you to create an individual regimen for using the drug for him and choose its optimal dose. Chronopharmacology helps improve the effectiveness and safety of drug use.

The theoretical basis of chronopharmacology is the presence of a biological pattern of oscillatory processes in any living systems. Cells, tissues, organs, physiological systems and the whole organism have periods of greatest vital (biological) activity, which are then replaced by periods of least activity. The oscillatory nature of the life of an entire organism can be demonstrated by the change from daytime activity to nighttime rest with a decrease in activity. Changes in the activity of chemical, biophysical and biochemical molecular processes in cells can occur in intervals of seconds and fractions of seconds. For example, at rest, with a heart rate of 60 per minute, an oscillation occurs in the myocardium, consisting of two phases (systole and diastole) for one second. The periods of biorhythms depend on genetic, functional and pathological processes.

In this regard, any biorhythm is characterized, in particular, by acrophase(period of greatest activity) and miniphase(period of least activity). As a rule, during the acrophase there is the greatest sensitivity and reactivity to stimulant drugs, and in the miniphase it is the least to stimulants and the greatest to depressants. In this regard, preparations of sex hormones and glucocorticoids prescribed on the principle of replacement therapy should be rationally administered in the morning, since the acrophase of the release of the corresponding hormones by the endocrine glands occurs in the morning hours of the day. In cases of other types of pathologies, the time of administration of the drug. The remedy is determined by the actrophase of a particular disease. For allergic diseases, it is more rational to administer glucocorticoid drugs in the evening hours to counter the acrophase of allergic pathology. The acrophase of pathology can occur several times a day. Therefore, it is advisable to administer the drug before the development of acrophase, so that the highest concentration coincides with the highest indicators (manifestations) of the disease. For example, in case of diabetes mellitus, hypoglycemic agents are administered 30-60 minutes before meals.

Thus, to judge the rational administration of drugs, one must know the physiological and pathological biorhythms with their acrophase and miniphase. Chronoesthesia- sensitivity of the body system depending on the time of day, year, etc. Chronergy-- reactivity of the system depending on the time of day, year, etc. Chronoesthesia and chronoergy to drugs that stimulate the central nervous system are greatest during the acrophase of the biorhythm of this physiological system. Chronoesthesia and chronergic reaction to drugs that inhibit the central nervous system are greatest in the miniphase of this physiological system. The practice of medicine raises the problem of changing the phase of chronoesthesia and the body's chronergic reaction to drugs. The theoretical approach to solving this problem is the position that biorhythms are an integral result of the interaction of hereditary properties and environmental factors. For example, ginseng preparations in the summer season do not cause a pronounced tonic effect in people, as is typical for them in the winter and autumn periods. Eleutherococcus in an average dose in experiments on frogs in summer causes inhibition of the central nervous system during ischemia, and in winter it increases the tone of the central nervous system and its resistance to ischemia. Analysis of this factor showed that reducing the dose by 10 times in the summer can produce an effect similar to the effect in the autumn-winter period. These differences are based on seasonal changes in chronoesthesia and chronoergy.

Biorhythms, heliogeophysical and environmental factors exert their influence on chronokinetics, chronometabolism, chronopharmacodynamics (of drugs) through the body’s regulatory systems. The main regulatory mechanism is the central nervous system, which changes the functions of the endocrine system and, together with it, influences the inheritance of the biorhythms of cells and tissues. As a result of this integration, signals are sent to change the “fate” of the drug in the body and change the sensitivity of receptors and the reactivity of cells and tissues. The interaction of chronokinetic chronometabolic processes, on the one hand, with chronopharmacodynamic processes, on the other hand, produces the final effect of changes in organ function, which is called a chronopositive or chrononegative effect.

Chronopharmacokinetics associated with the alternation of sleep and wakefulness, the biorhythms of the circulatory and digestive systems. The processes of drug metabolism are associated with general metabolism in the gastrointestinal tract, liver and other tissues. The most favorable period of the day for pharmacokinetics is the morning hours (from 7 to 12), especially the time 30-60 minutes before breakfast, when the gastrointestinal tract is free of food, or the time 2-3 hours after breakfast, when Digestive processes slow down in the stomach and intestines. In the morning hours, the processes of absorption and transport of substances to organs are more active, thanks to the increasing activity of the central nervous system of the heart, respiration, increased body movements, which together enhances blood circulation - the main factor in ensuring pharmacokinetics. The content of medicinal substances in the blood in the morning is also increased due to their slower metabolism due to reduced body temperature, which by 18 o'clock increases by 1-1.5 "C. For example, the peak concentration in blood plasma in the morning (from 7 to 11) is observed for acetylsalicylic acid, indomethacin, amidopyrine, erythromycin, ampicillin.

For the development of a pharmacological reaction, the concentration of the substance in the tissue and cell is essential. The absorption of a drug into the blood and its penetration from the blood into tissues and cells is regulated by the sympathetic nervous system. It reaches its greatest activity at 18:00, then decreases and begins to increase again in the morning. As its activity increases, absorption decreases. B-adrenergic receptor blockers increase absorption and increase the transfer of substances from the blood to the tissues. At the same time, increased tone of the sympathetic system increases the metabolism of substances, for example, acetylation of sulfonamides. Therefore, in early spring, when the activity of the sympathetic nervous system increases, increased acetylation of substances is produced, which can be reduced with B-blockers. Thus, from the point of view of chronopharmacokinetics, the second half of the day is less favorable for taking medications. This pattern only indicates that, if it is necessary to use drugs in the evening or at night, the standard dose can be used or exceeded.

Chronopharmacodynamics studies the dependence of the pharmacotherapeutic effect of a medicinal substance on circadian and other rhythms, in particular on sensitivity to the substance at different times of the day. With an increase in the body's chronoesthesia, a sufficient therapeutic effect occurs when the average dose is reduced.

There is no deterministic relationship between chronopharmacodynamics, chronopharmacokinetics and chronometabolism of drugs, since these phenomena occur with the participation of different processes in different systems. Therefore, the determining factor for establishing the optimal time for taking a drug is the periodicity of the disease phases. For example, if a patient’s body temperature rises at 5-6 p.m., then antipyretics should be prescribed at 4-5 p.m., despite the fact that their pharmacokinetics are more optimal in the morning. When the period of optimal pharmacokinetics likely coincides with the acrophase of a physiological or pathological system, then even a small dose can produce a preventive or therapeutic effect. For example, just 40 mg of acetylsalicylic acid is enough to take in the morning on an empty stomach to reduce platelet aggregation.

Desynchronoses are biorhythm disorders. They occur when working at night, moving from one time zone to another and during illness. When the time of day changes, the previously developed acrophase of activity changes to the mini-phase of rest (sleep). At the same time, a new adaptive biorhythm of all physiological systems of the body is formed under the influence of motor and nervous activity, environmental conditions and the influence of daylight hours.

The process of normalization (synchronization) of disturbed biorhythms can be accelerated by means that increase the body’s adaptation and resistance: central nervous system tonics (ginseng preparations, eleutherococcus, etc.); means that improve metabolism (vitamin and coenzyme preparations); cell membrane stabilizers (antioxidants).

• 1. The concept of treatment as a targeted correction of physiological disorders in the body. Benefits and risks of using medications. Reasons for their use. Safety assessment.
• 2. The essence of pharmacology as a science. Sections and areas of modern pharmacology. Basic terms and concepts of pharmacology - pharmacological activity, action, effectiveness of chemicals.
• 3. Chemical nature of drugs. Factors that provide the therapeutic effect of drugs are pharmacological action and placebo effects.
• 5. Routes of administration of drugs into the body and their characteristics. Presystemic drug elimination.
• 6. Transfer of drugs through biological barriers and its varieties. The main factors influencing the transport of drugs in the body.
• 7. Transfer of drugs through membranes with variable ionization (Henderson-Hasselbalch ionization equation). Principles of transfer management.
• 8. Transfer of drugs in the body. Water diffusion and diffusion in lipids (Fick's law). Active transport.
• 9. The central postulate of pharmacokinetics is the concentration of a drug in the blood - the main parameter for controlling the therapeutic effect. Problems solved on the basis of knowledge of this postulate.
• 10. Bioavailability of drugs - definition, essence, quantitative expression, determinants. The concept of bioavailability
• 11. Distribution of drugs in the body. Compartments, ligands. Main determinants of distribution.
• Distribution compartments:
• Molecular ligands of drugs:
• 12. Elimination constant, its essence, dimension, relationship with other pharmacokinetic parameters.
• 13. Half-life of drugs, its essence, dimension, relationship with other pharmacokinetic parameters.
• The half-life is the most important pharmacokinetic parameter, allowing:
• 14. Clearance as the main pharmacokinetic parameter for controlling the dosage regimen. Its essence, dimension and relationship with other pharmacokinetic indicators.
• 15. Dose. Types of doses. Drug dosage units. Purposes of drug dosing, methods and options of administration, interval of administration.
• 16. Administration of drugs at a constant rate. Kinetics of drug concentration in the blood. Stationary concentration of the drug in the blood (Css), time to reach it, calculation and management of it.
• 18. Introductory (loading) dose. Therapeutic meaning, calculation of pharmacokinetic parameters, conditions and limitations of its use.
• 19. Maintenance doses, their therapeutic meaning and calculation for the optimal dosage regimen.
• 20. Individual, age and sex differences in the pharmacokinetics of drugs. Adjustments for calculating individual drug volume of distribution values.
• 21. Renal clearance of drugs, mechanisms, their quantitative and qualitative characteristics.
• 22. Factors affecting renal clearance of drugs. Dependence of clearance on the physicochemical properties of drugs.
• 23. Hepatic clearance of drugs, its determinants and limitations. Enterohepatic cycle of drugs.
• 24. Correction of drug therapy for liver and kidney diseases. General approaches. Correction of the dosage regimen under the control of the total clearance of the drug.
• 25. Correction of drug therapy for liver damage and dosage regimen under the control of residual renal function.
• 26. Factors that change the clearance of drugs. Strategy for individual drug therapy.
• 27. Biotransformation of drugs, its biological meaning, main focus and influence on the activity of drugs. The main phases of metabolic transformations of drugs in the body.
• 29. Pathways and mechanisms for removing drugs from the body. Possibilities for controlling drug excretion.
• Possibilities for managing drug removal processes:
• 30. The concept of receptors in pharmacology, the molecular nature of receptors, signaling mechanisms of drug action (types of transmembrane signaling and second messengers).
• 31. Physico-chemical and chemical mechanisms of action of medicinal substances.
• 32. Terms and concepts of quantitative pharmacology: effect, effectiveness, activity, agonist (full, partial), antagonist. Clinical difference between the concepts of activity and effectiveness of drugs.
• 35. Types of action of drugs. Changes in the effect of drugs upon repeated administration.
• 36. Dependence of the effect of drugs on age, gender and individual characteristics of the body. The meaning of circadian rhythms.
• Reasons for variability in the effects of drugs:
• 38. Assessing drug safety. Therapeutic index and standard safety margins.
• 39. Pharmacokinetic interaction of drugs
• 1) At the suction stage.
• 2) Upon distribution and deposit:
• 3) During metabolism
• 40. Pharmacodynamic interaction of drugs. Antagonism, synergism, their types. The nature of changes in the effect of drugs (activity, effectiveness) depending on the type of antagonism.
• 41. Side and toxic effects of drugs. Teratogenic, embryotoxic, mutagenic effects of drugs.
• 45. Medical and social aspects of the fight against drug addiction, drug addiction and alcoholism. The concept of substance abuse.
• 43. Kharkevich’s textbook, p.69
• 44. Types of pharmacotherapy. Deontological problems of pharmacotherapy.
• 45. Basic principles of treatment and prevention of drug poisoning. Antidote therapy.
• II. Delayed absorption and removal from the body of unabsorbed substances:
• III. Removal of absorbed oats from the body
• IV. Symptomatic treatment of functional disorders.
• 46. ​​Recipe and its structure. General rules for writing a prescription. State regulation of the rules for prescribing and dispensing drugs.

• A) by age: in children and the elderly, sensitivity to drugs is increased (because in children there is a deficiency of many enzymes, kidney function, increased permeability of the blood-brain barrier, in old age the absorption of drugs is slower, metabolism is less efficient, the rate of excretion of drugs by the kidneys is reduced):

  1. In newborns, sensitivity to cardiac glycosides is reduced, because they have more Na + /K + -ATPases (targets of glycoside action) per unit area of ​​the cardiomyocyte. 2. Children have lower sensitivity to succinylcholine and atracurium, but increased sensitivity to all other muscle relaxants. 3. Psychotropic drugs can cause abnormal reactions in children: psychostimulants can increase concentration and reduce motor hyperactivity, tranquilizers, on the contrary, can cause the so-called. atypical excitement.

  1. Sensitivity to cardiac glycosides sharply increases due to a decrease in the number of Na + /K + -ATPases. 2. Sensitivity to β-blockers decreases. 3. Increases sensitivity to calcium channel blockers, because The baroreflex is weakened. 4. There is an atypical reaction to psychotropic drugs, similar to the reaction of children.

  b) from the floor:

  1) antihypertensive drugs - clonidine, β-blockers, diuretics can cause sexual dysfunction in men, but do not affect the functioning of the reproductive system of women.

  2) anabolic steroids cause a greater effect in the body of women than in the body of men.

  V) from the individual characteristics of the body: deficiency or excess of certain enzymes of drug metabolism leads to an increase or decrease in their action (deficiency of blood pseudocholinesterase - abnormally prolonged muscle relaxation when using succinylcholine)

  G) from circadian rhythms: change in the effect of a drug on the body quantitatively and qualitatively depending on the time of day (maximum effect at maximum activity).

  37. Variability and variability of drug effects. Hypo- and hyperreactivity, tolerance and tachyphylaxis, hypersensitivity and idiosyncrasy. Reasons for variability in drug action and rational treatment strategy.

  Variability reflects differences between individuals in response to a given drug.

  Reasons for variability in the effects of drugs:

  1) change in the concentration of a substance in the receptor area - due to differences in the rate of absorption, its distribution, metabolism, elimination

  2) variations in the concentration of the endogenous receptor ligand - propranolol (a β-blocker) slows heart rate in people with elevated levels of catecholamines in the blood, but does not affect the background heart rate in athletes.

  3) change in receptor density or function.

  4) changes in reaction components located distal to the receptor.

  Rational therapy strategy: prescription and dosage of drugs, taking into account the above reasons for the variability of drug action.

  Hyporesponsiveness– a decrease in the effect of a given dose of a drug compared to the effect that is observed in most patients. Hyper-reactivity- increasing the effect of a given dose of medicine compared to the effect that is observed in most patients.

  Tolerance, tachyphylaxis, hypersensitivity – see section 38

  Idiosyncrasy– a perverted reaction of the body to a given drug, associated with the genetic characteristics of drug metabolism or with individual immunological reactivity, incl. with allergic reactions.

Pathology (Greek pathos suffering, disease + logos doctrine) is the science of the patterns of occurrence, course and outcome of diseases, based on factual material from various medical and biological disciplines. Each of these disciplines records one or another aspect of human diseases: pa...

The diaphragm (diaphragma septum; synonym: thoraco-abdominal barrier) is a muscular aponeurotic formation that separates the thoracic cavity from the abdominal cavity. It is a flat, thin muscle that has the shape of a dome, convexly facing upward and covered with a parietal layer of pleura (...

News about Chronopharmacology

• A. N. Britov Doctor of Medical Sciences, Professor, Head of the Department of Prevention of Internal Diseases, State Research Center for Preventive Medicine, Ministry of Health of the Russian Federation Essentially, any therapy should begin with modification of the patient’s lifestyle. This comes down to dietary correction, correction of motor activity
• Professor O.V. Zaitseva RGMU Respiratory diseases are one of the most important problems in pediatrics, occupying one of the first places in the structure of childhood morbidity. Among the main factors in the pathogenesis of inflammatory respiratory diseases is a violation of the mucosal mechanism

Discussion Chronopharmacology

• Hello! Tell me where I can “enlighten myself” on biorhythms. The fact is that my mother (54 years old) very often wakes up at night at the same time. So, she asked me to find out at what time which organ starts working. I don't understand anything about this. Please advise something or where to look. Saved

Dependence of medicinal substances on internal factors (age and gender; pathological state of organs and systems that determine homeostasis). The concept of chronopharmacology. The influence of biological rhythms on the action of drugs.

A) AGE Sensitivity to drugs varies depending on age. In this regard, the so-called perinatal pharmacology emerged,

This is due to the deficiency of many enzymes, kidney function, increased permeability of the blood-brain barrier, and underdevelopment of the central nervous system. Receptors during this period of life also have a different sensitivity to drugs.

Thus, the use of morphine (due to the immaturity of the blood-brain barrier) and topical use of dicaine (due to the high permeability of the mucous membranes and increased sensitivity to the toxic effect of the drug) are contraindicated for children under 5 years of age.

The area of ​​pharmacology that studies the characteristics of the action of substances on the children's body is called pediatric pharmacology.

Clarification of the characteristics of the action and use of medicines in elderly and senile people.

B) GENDER: In an experiment on animals, it was shown that males are less sensitive to a number of substances than females. Gender-related differences in the metabolism of a number of substances have also been noted.

B) GENETIC FACTORS

Sensitivity to drugs may be genetically determined. This manifests itself both quantitatively and qualitatively.

There are known examples of atypical reactions to substances.

Determining the role of genetic factors in the body's sensitivity to drugs is the main task of a special field of pharmacology - pharmacogenetics

D) STATE OF THE BODY

The effect of drugs may depend on the condition of the body, in particular, the pathology against which they are prescribed.

Diseases accompanied by impaired renal or liver function alter the excretion and biotransformation of substances accordingly. The pharmacokinetics of drugs changes during pregnancy and obesity.

Circadian rhythms are important for physiological functions. It is well known that the alternation of wakefulness and sleep significantly affects the activity of the nervous system and endocrine glands and, accordingly, the state of other organs and systems. In turn, this affects the body’s sensitivity to various substances. The study of the dependence of the pharmacological effect on daily periodicity is one of the main tasks of a new direction called chronopharmacology. The latter includes both chronopharmacodynamics and chronopharmacokinetics,

Depending on the time of day, the effect of substances can change not only quantitatively, but sometimes also qualitatively. In humans, the painkiller morphine is more active in the early afternoon than in the early morning or at night. For angina pectoris, nitroglycerin is more effective in the morning than in the afternoon.

Depending on the daily periodicity, the toxicity of substances also changes significantly. In experiments on animals at different times of the day, the lethal effect of phenobarbital in a toxic dose ranges from 0 to 100%. Kidney function and their ability to excrete pharmacological agents change depending on the time of day. For phenamine, they are excreted by the kidneys in the early morning for the phases and amplitude of the circadian rhythm. for various pathological conditions and diseases.

Chronopharmacology is a branch of pharmacology that studies the variability of pharmacodynamic and pharmacokinetic parameters depending on the time of administration of the drug (period of day, month, season of the year, etc.). The goal of chronopharmacology is to optimize pharmacotherapy by reducing single, daily, course doses of drugs, reducing the severity of side effects (taking into account the time of drug use).

Several years ago, calculations of personal biorhythms - cycles of activity and passivity in the physical, intellectual and emotional spheres - were fashionable. The starting point for such calculations is the date of birth. How objective is this? PHYSICAL ACTIVITY, MENTAL ACTIVITY, EMOTIONAL ACTIVITY

Biological rhythm is a fundamental property of all living systems, ensuring the organism’s adaptation to the external environment. Under the influence of constantly repeating influences of environmental factors that form exogenous rhythms, in the process of evolution, structural and functional organizations arose in living systems that implement endogenous rhythms. Initially, cellular metabolic biorhythms were formed, “basic” in their essence. Subsequently, in the course of evolution, “superstructural” biorhythms were formed associated with the gradual activation of regulatory systems: immune, endocrine, and nervous. As a result of natural selection, endogenous biorhythms became fixed in the gene.

In the human body there are more than 500 biorhythms, functioning at a variety of levels - cellular, tissue, organ, organismal. Each of them has a wide range of periods - from a thousandth of a second to several years. There are: low-, medium- and high-frequency biorhythms.

Many rhythms have the word "circus" in their names. The Latin word "circa" translates as "around, around, approximately", and all biorhythms have periods close to our calendar intervals, but do not coincide with them.

Src="https://present5.com/presentation/3/134159628_437415429.pdf-img/134159628_437415429.pdf-8.jpg" alt="Low-frequency biorhythms (T > 3 days) circaseptal (7± 3 days ), circadian (14 ± 3 days),"> Низкочастотные биоритмы (Т > 3 суток) циркасептанные (7± 3 суток), циркадисептанные (14± 3 суток), циркавигинтанные (21± 3 суток), циркатригинтанные (30± 5 суток) и цирканнуальные (1 год± 2 месяца). В эту же группу входят макроритмы, связанные с циклами солнечной активности, их периоды - от 2 до 35 лет.!}

Mid-frequency rhythms (T from 30 minutes to three days): ultradian (30 minutes - 20 hours), circadian (circadian, 24 - 28 hours), infradian (28 hours - 3 days). Circadian rhythms are determined by the ionic function of the kidneys, as well as the synthesis of ADH, aldosterone, protein and glycogen.

High frequency rhythms (T

The most important thing for the human body is the circadian biorhythm. It is associated with cycles of activity and relative rest of all our internal organs and systems, as well as the cyclic synthesis of metabolites and metabolic processes. Therefore, prolonged disruption of the circadian rhythm (for example, the inability to get enough sleep or maintain a normal diet) negatively affects well-being and even leads to serious illnesses.

The picture of human health is not a “frozen snapshot,” but a living, constantly changing “picture on the TV screen.” For example: In the morning - one blood pressure, in the evening - completely different, At night - one panorama of hormonal activity, during the day - another, At noon - one physical condition, in the evening - completely different.

Today, the most reliable is considered not a second snapshot of the state, not quantitative measurements, but long-term monitoring of health indicators and its qualitative characteristics. That is why studies are carried out using monitors - miniature portable devices that reflect the work of the body in real time, or repeated cartogram analyses. Even at home, the doctor will recommend not just regularly measuring blood pressure, for example, but measuring it three times a day - at the same time, under the same conditions - and carefully recording this data. This is the only way to identify the true nature of your hypertension and choose the right medications.

TERMINOLOGY Chronotherapy is a therapy based on an understanding of the body's biorhythms. Chronopharmacotherapy is the study of the effect of medicinal substances on the body's biorhythms and their effectiveness depending on the time of administration. 3 methods of chronopharmacology - imitation, preventive, imposing the correct rhythm, determining chronosensitivity. Chronopharmacology - the basis of chronotherapy CHRONOTHERAPY Chronopharmacology

1. Imitation method - allows you to imitate normal metabolic processes in the body, which the disease has either broken completely or made insufficiently active. The method is based on established patterns of changes in the concentration of certain substances in the blood and tissues in accordance with the biorhythm characteristic of a healthy individual. This method is successfully used in therapy with various hormonal drugs. EXAMPLE: bronchial patency is higher during the day than at night. It is directly dependent on the activity of the adrenal cortex. In bronchial asthma, bronchial resistance is minimal at 12 noon and maximum at midnight. Therefore, to prevent asthma attacks, doctors often recommend taking bronchodilators at night: at 20-22 hours.

ANOTHER EXAMPLE: Among drugs used taking into account the circadian rhythm, corticosteroids attract the most attention. It was for therapy with these hormones that a simulation method was developed, since it was found that minimal changes in the function of the adrenal cortex are observed when corticosteroids are prescribed only in accordance with the natural daily rhythm of their secretion and excretion. If glucocorticoids are used outside of acrophase, especially in the evening and night hours, this leads to an increase in their catabolic effect, a decrease in body weight and adrenal mass, and a sharp disruption of the circadian rhythm of the adrenal cortex.

When treating with corticosteroids, the opposite direction of action of cortisol and aldosterone, which are antagonists, is taken into account. In this regard, the activity of mineralocorticoids (pro-inflammatory hormones) can be suppressed by the introduction of an adequate dose of glucocorticoids (anti-inflammatory hormones) in the second half of the day. In this case, it is necessary to take into account the half-life of glucocorticoid drugs: 90 minutes for hydrocortisone, 3 hours for prednisolone. During replacement therapy, glucocorticoids are prescribed in the morning (at 6-7 o'clock). Thus, the daily rhythm of cortisol synthesis is simulated and the time of greatest need for it is taken into account.

2. Prophylactic (preventive) method - the method is based on the idea that the maximum effectiveness of drugs coincides with the acrophase (time of maximum value) of the indicators. This idea is based on the law of J. W i l d e r (1962), according to which the function is less stimulated and more easily suppressed, the more strongly it is initially activated. Optimizing the timing of drug administration is based on calculating the time required to create the maximum concentration of the drug in the blood by the time a certain event occurs. How is this done? First, the acrophase of pathological processes in the body is determined, and then the necessary medications are prescribed at this time or a few hours before the acrophase

EXAMPLE: NSAIDs are more effective in the afternoon and evening. For example, in patients with rheumatoid arthritis, NSAIDs relieve pain faster and normalize body temperature if taken after lunch. But if the acrophase of body temperature is observed after noon and before six o’clock in the evening, and the pain is worse in the evening, then the medicine is recommended to be taken at noon. And for those who have pain at night, medications are prescribed at 19:00.

Hypertension therapy - based on round-the-clock determination of blood pressure (data from 24-hour blood pressure monitoring (ABPM)), its circadian profile and the optimal time for taking medications are established. They are prescribed taking into account blood pressure peaks and the pharmacokinetics of the drugs used so that the expected maximum antihypertensive effect occurs during periods of the day with the highest blood pressure values. 1. Every morning, a doctor who is a “morning person” records the patient’s blood pressure as 160 mm. rt. Art. Both are worried. 3. A methodical “turtle” doctor measures the daily blood pressure profile and selects the correct treatment.

Hypertension therapy - The use of antihypertensive drugs 1.5-2 hours before the acrophase of systolic blood pressure and cardiac output or cardiac index established during the first biorhythmological study made it possible to achieve a reduction in blood pressure in a shorter time (2 times) using smaller one-time, daily and course doses (2-3 times) of the corresponding drugs than with traditional treatment (1 tablet 2-3 times a day)

3. Method of imposing rhythms - simultaneously blocks pathological, “wrong” rhythms (desynchronoses) formed by the disease, and with the help of medications forms rhythms close to normal. The so-called pulse therapy of many chronic diseases is based on this approach. This is the use of drugs in precisely calculated doses in an equally precisely calculated rhythm, which imitates the correct metabolic processes, increasing the patient’s quality of life. This method takes into account those periods of the daily blood pressure profile when blood pressure values ​​are “normal”, for example, during sleep in some “dipper” patients and in “over-dippers”.

For most healthy people, a nighttime decrease in blood pressure by 10-22% is typical. Patients with a daily index (DI) of 10-22% are called dippers; they have a blood pressure profile that deepens at night and has the shape of a bucket (dipp in English transcription). Less common are patients whose blood pressure decreases less at night or does not decrease at all (CI 0 -9%) - the non-dippers category. There are also patients with an excessive drop in blood pressure at night - over-dippers, with a daily index above 22%. Patients with a rise in blood pressure at night above the daytime level are classified as night peakers; the daily index has a negative value.

The type of antihypertensive drugs (AHDs) (short-acting or long-acting), the time and frequency of their administration are selected so that during periods of the day with normal or minimally elevated blood pressure values, the drug does not have a hypotensive effect or it is minimal. This helps avoid drug-induced hypotension

4. Determination of chronosensitivity Example - determination of chronosensitivity to an antihypertensive drug: It is prescribed at different times of the day and clinical and pharmacological studies are carried out over several days to determine the optimal time for taking the drug. In patients with increased blood pressure not only during the day, but also at night, drugs and forms with a prolonged effect have a clear advantage.

However, in those patients in whom a reduction in relatively low or normal nocturnal blood pressure is not desired due to the risk of deterioration of coronary, cerebral or renal blood flow and the development of associated complications, preference should be given to short-acting drugs, prescribing them in the first half of the day and avoiding use at night. A number of researchers associate an increase in the frequency of strokes, heart attacks, anginal attacks and cases of sudden death with a rapid and significant increase in blood pressure in the morning. Chronotherapy with antihypertensive drugs allows you to reduce the rate and magnitude of the rise in blood pressure in the morning.

CHRONOPHARMACOLOGY - THEORY Chronotherapists do not just treat a disease, they treat it taking into account biological rhythms. In Russia, chronomedicine is developing rapidly and intensively. Many developments of our scientists allow us to improve diagnostic and treatment methods and are recognized as a priority. Specialists in chronopharmacology: R. M. Zaslavskaya O. N. Davydova and others.

CHRONOPHARMACOLOGY - PRACTICE If you ask an ordinary doctor if he knows anything “about the biological clock,” you will usually get the answer: yes, there is something elusive that seems to exist. But at the same time, doctors and biologists have already appeared in the scientific world, insisting that each organism has its own biological clock. Moreover, some neurosurgeons argue that the biological clock is a collection of nerve cells in the hypothalamus region (at the base of the brain). Thus, we can say that an anatomical structure has been found that is responsible for the regulation of the physiological and mental activity of the body over time.

The same surgeons noticed a certain connection between the time of the operation and its success. In the United States in the 1990s, 1,000 women with breast cancer who had undergone breast removal were observed. The results were significantly better in women operated on around day 14 of the menstrual cycle.

Scientific confirmation of the theory of chronopharmacology The hypothalamus-pituitary-adrenal system controls the entire body; thanks to neuroendocrine regulation, a person maintains a constant body temperature, heart rate, and blood pressure. An important role in this process is played by the same accumulation of nerve cells in the hypothalamus, which neurosurgeons consider to be a biological clock. When the rhythmic activity of the biological clock is disrupted (during long flights, especially when crossing time zones, insomnia, stress), health faces a very real danger.

Researchers from Seattle found that after 3 years of work, women who work nights are 40% more likely to be diagnosed with breast cancer than those who work only during the day. The explanation for this phenomenon is quite simple. Artificial light disrupts the action of the biological clock and reduces the level of melatonin, which is involved in the regulation of sleep and wakefulness. All this, in turn, increases the level of estrogen, which ultimately contributes to the occurrence of breast cancer. The presence of individual biological clocks is also confirmed by the division of people into owls and larks, or, conversely, such a difference between people suggests that biological clocks do exist

Scientists at Stanford University have discovered genes that determine whether a person is a morning person or a night owl. You can influence the manifestations of these genes; you can even force yourself to go against your nature through an effort of will. But it is impossible to change. Most women give birth between midnight and six in the morning, and menstruation, as a rule, begins between six in the morning and noon. Migraine, epileptoid and even diabetic attacks most often occur immediately before menstruation. American chronobiologists advise women to keep a menstrual calendar, regularly noting the most unsuccessful physiological and emotional plan days, and try to contact your doctor at the peak of physical ailments.

The biological clock is controlled by certain genes in the body. And subconsciously our body, as a biological structure, tries to live in accordance with this clock. At the same time, man is a social being, dependent on social life, and this dependence forces us, by drowning out the biological clock, to try to live contrary to genetic predetermination.

Advice from chronopharmacologists 24 hours from the life of your body (average data). 7 -8 o'clock in the morning. Do not work, at this time of day the body is not inclined to hard or strenuous work. You need to lie stretched out for a while, stretching and then relaxing your muscles - the body should calmly perceive the signals coming from the spinal cord. Have a leisurely breakfast. In the morning, you can eat almost anything you want; the calories you accumulated will be spent over the long day ahead. 8 -10 o'clock in the morning. Everything is strictly individual: larks can work quite intensively, owls gradually immerse themselves in work. 10 -12 hours. Peak mental performance - any difficult job that requires concentration, creativity or memorization is performed well.

12 -13 hours. Larks experience some decline in activity and slight fatigue, owls continue to work actively. 13-15 hours. Time relax. Mental activity decreases, although long-term memory works well. If rest is not possible, review something important, flip through your exam textbook. At the same time, the perception of pain is also reduced, so feel free to plan a visit to the dentist. 15 -16 hours. You can have a little snack and take a break.

16 -19 hours. It's time to hit the gym: now your joints are most mobile, your muscles are strong, and your attention is focused. Scientists have found that muscles are 20% stronger in those who exercise in the evening compared to those who perform the same exercises in the morning. These same hours are most favorable for conception. 19 -20 hours. Pleasant idleness. The lightest dinner. 20 o'clock - midnight. It's time to take care of your skin: at this time, all creams are absorbed 20% more efficiently. Owls can think over creative plans, larks can devote an hour to household chores. Midnight - 7 am. Healthy sleep.

Women's calendar 7-14 days - time for self-monitoring of breast condition: at this time, neoplasms are most easily identified. During these days, water retention in the body can make your weight slightly heavier than usual. Day 14 or 15 - ovulation. During this period, it is advisable to undergo medical examinations. At this time, tumor cells are easier to detect. But do not do tests related to bronchial asthma. During ovulation, the result will obviously be worse than it really is. 15 -22 day. The best time for operations. At this time, the threshold of pain sensitivity increases significantly and the procedure will be almost painless. The best period for conception. 23 -27 days. Eat more vegetables and fruits and drink water. Prepare your body for the start of the next cycle.