Check for drug interactions. What foods and drinks should not be combined with medications? Blood pressure pills and antibiotics

1. Green color - medications are compatible
2. Red color - medications are not compatible
3. Yellow- you need to click on the yellow field and read the recommendation.

IMPORTANT! Compatibility is ALWAYS checked active ingredient in medicine, not the name of the drug.

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ATTENTION! The compatibility table is given for informational purposes only and is not a guide to action; for all questions about the compatibility of drugs during therapy, you should consult your doctor. We DO NOT answer questions about the compatibility of medications during therapy. Thanks for understanding.

Interactions between direct acting inhibitors (HCV DAAs) and drugs used for cardiovascular diseases

Green: No clinically significant interaction detected
Yellow: adjustment of the dose and timing of the drug may be necessary, additional monitoring is necessary
Red: taking drugs together is prohibited

The table describes:
Interactions of drugs used for cardiovascular diseases: antiarrhythmic drugs (Amiodarone, Digoxin, Flecainide, Vernakalant), antiplatelet drugs and anticoagulants (Clopidogrel, Dabigatran, Warfarin), beta blockers (Atenolol, Bisoprolol, Propranolol), calcium channel blockers (Amlodipine, Diltiazem, Nifedipine), drugs for hypertension and heart failure (Aliskiren, Candesartan, Doxazosin, Enalapril)
And

Interaction between direct acting inhibitors (HCV DAAs) and immunosuppressants.
(European Association for the Study of Liver Diseases Guidelines)

The table describes:
Interaction of immunosuppressants: Azathioprine, Cyclosporine, Etanercept, Everolimus, Mycophenolate mofetil, Sirolimus, Tacrolimus and Direct acting antiviral drugs against hepatitis C: Simeprevir, Daclatasvir, Sofosbuvir, Ledipasvir, Viqueira Pak combination (ombitasvir+paritaprevir+dasabuvir+ritonavir)
(Immunosuppressive drugs are used primarily in organ and tissue transplantation, such as kidneys, heart, liver, lungs, bone marrow)

Interaction between direct acting inhibitors (HCV DAAs) and antiretroviral drugs (Hepatitis C + HIV)
(European Association for the Study of Liver Diseases Guidelines)

The table describes:
Drug interactions for HIV antiretroviral therapy: Abacavir abacavir, Didanosine didanosine, Emtricitabine emtricitabine, Lamivudine lamivudine, Stavudine stavudine, Tenofovir tenofovir, Zidovudine zidovudine, Efavirenz efavirenz, Etravirine etravirine, Nevirapine nevirapine, Rilpivirine rilpivirine, Atazanavir atazanavir, Atazanavir/ ritonavir atazanavir/ritonavir, Darunavir/ritonavir darunavir/ritonavir, darunavir/cobicistat darunavir/cobicistat, Fosamprenavir fosamprenavir, Lopinavir lopinavir, Saquinavir saquinavir, Dolutegravir dolutegravir, Elvitegravir/cobicistat elvitegravir/cobicistat, Maraviroc maraviroc and Direct acting antiviral drugs against hepatitis C: Simeprevir, Daclatasvir, Sofosbuvir, Ledipasvir, Viqueira Pak combination (ombitasvir + paritaprevir + dasabuvir + ritonavir).

Before taking any medications in therapy in parallel with sofosbuvir, daclatasvir (ledipasvir, velpatasvir), you must check their compatibility. Some medications, such as some types of antibiotics, may reduce the therapeutic benefit or may increase side effects.

For example, medications such as the antibiotic levomecitin, the anti-tuberculosis drug riafampicin, herbal infusions (St. John's wort, milk thistle, etc.) will weaken the effect of sofosbuvir, therefore their parallel use in therapy is not recommended.

During therapy, it is prohibited to take any hepatoprotectors (milk thistle, karsil, heptral, phosphoglyph.

Sorbents such as activated carbon, polysorb and others can be taken at least 3 hours before and after taking sofosbuvir daclatasvir.

Omez, omeprozole should be taken at least 6 hours before or after taking inhibitors.

Compatibility Database Instructions:

1. GREEN color - medications are compatible
2. RED color - medications are not compatible
3. Yellow color - you need to click on the yellow field and read the recommendation.

ATTENTION! The compatibility table is given for informational purposes only and is not a guide to action; for all questions about the compatibility of drugs during therapy, you should consult your doctor. We DO NOT answer questions about the compatibility of medications during therapy.

We all know that you should not mix medications with alcohol, tea, or coffee. But few people know which medications should not be taken in pairs, because this can cause severe harm to health, and the worst thing is lead to death.

Unfortunately, this information is not widely distributed, but every person taking any medication should know this. Editorial "So simple!" will tell you about 5 destructive drug combinations. Remember and never do that!

Combination of drugs

1. Antidepressants and painkillers
   A person to whom a doctor has written a prescription for this group of drugs knows that they cannot be taken together. But how often do we neglect consultation with competent people and simply go to the pharmacy to buy an inexpensive life-saving remedy.

   

   A recent study by Dutch doctors showed that taking a combination of these two drugs provokes gastrointestinal bleeding. But the result of their interaction is not only the danger of internal bleeding, but also unpleasant side effects: anxiety, increased body temperature, rapid heartbeat and breathing.
   
   

2. Cough and allergy medicine
   Most cough and allergy medications contain similar substances, so if you take both remedies together, you risk getting an excess dose. And this will significantly increase the sedative effect - the feeling of weakness and fatigue.

   

   Uncontrollable drowsiness may pose a risk to those who, unaware of the sedative effects of this combination, operate dangerous equipment, machinery, or drive a vehicle.
   
   

3. Anticoagulants and aspirin
   Anticoagulants are considered quite serious medications and are sold only with a doctor's prescription. They are prescribed to reduce the formation of blood clots in the arteries. But aspirin can be bought at any pharmacy without a prescription. We take it as a remedy for pain, add it to cosmetics, and use it in everyday life.

   

   However, many do not know that this drug also thins the blood and is known as an antiplatelet agent. When aspirin is taken along with an anticoagulant, their combined effect can significantly increase the chances of developing internal and external bleeding.
   
   

4. Painkillers and sedatives
   If these drugs are taken at the same time, their toxic effect increases. Such an overdose of antidepressants can significantly reduce both breathing and heart rate, sometimes to fatal levels.
   
   
5. Acetaminophen and opioids
   Despite their popularity, these drugs can be very dangerous if taken in quantities greater than the recommended dose. People often try to increase the effect of acetaminophen by taking it with codeine-containing medications. When these medications are taken together, they can cause serious liver damage very quickly.
   
   

In drug treatment, combinations of drugs are often used to enhance the effect of one drug with another, limit the dose of each of them, and reduce side effects; for polysyndromic manifestations of the disease - to influence a number of pathogenesis mechanisms, correct changes that have occurred, and alleviate all existing complaints; in the presence of several diseases - for simultaneous treatment of each of them. Since the side effects characteristic of certain medications are known, it is possible to prevent these undesirable consequences of treatment by prescribing protective drugs: treatment with glucocorticoids should be carried out under the protection of antibiotics, antacids, and anabolic agents; Due to the risk of developing dysbiosis, antimicrobial antibiotics should be combined with nystatin or other antifungal drugs. The successes of differentiated pharmacotherapy are increasingly increasing the list of possible and desirable areas of treatment. But therapeutic activity threatens to turn into polypharmacy with its many dangers, the most obvious of which is drug incompatibility.

There are three types of incompatibility of medicinal prescriptions: physical (or physicochemical), chemical and pharmacological. Physical incompatibilities include those that depend on different degrees of solubility of drugs, coagulation of colloidal systems and separation of emulsions, dampening and melting of powders, adsorption phenomena (Table 3).

Table 3. Formation of sediment when combining alkaloid drugs (in 1% solution) with other medicinal substances [Muravyov I. A., Kozmin V. D., Kudrin A. N., 1978]

Chemical incompatibility arises as a result of reactions that occur when solutions are combined in the same volume. They are prevented by separate administration of drugs.

The options for pharmacological incompatibility caused by the interaction of the effects of drugs when used simultaneously are much more diverse and complex.

Information regarding physical and chemical incompatibility is included in prescription reference books, bulletins, and tables. Prescriptions are controlled when filling out a prescription in pharmacies. However, in everyday practice, due to insufficient awareness of doctors and medical personnel, deviations from approved recommendations are often made with negative consequences for the patient.

When a patient takes several tablets at the same time, not only their pharmacological incompatibility is possible, but also chemical interaction in the gastrointestinal tract in conditions where digestive juices and other ingredients of chyme become biological catalysts for the reactions that occur.

Pharmacological incompatibility has various causes and forms. Antagonistic (or absolute) incompatibility is possible in cases where drugs have multidirectional effects on processes occurring in a cell, tissue, organ or whole organism, and the effect of one is suppressed by the effect of the other. This type of incompatibility is successfully used in the treatment of poisoning when the drug is administered as an antidote: for example, atropine for poisoning with cholinesterase inhibitors, organophosphorus substances, fly agaric (muscarine), pilocarpine; on the contrary, pilocarpine, proserine, physostigmine - in case of atropine poisoning.

Incompatibility also arises between synergists due to the fact that the risk of overdose or increased side effects increases disproportionately. The simultaneous administration of a beta-blocker, digoxin and reserpine causes bradycardia, conduction disturbances, and threatens the development of arrhythmias; administration of strophanthin during treatment with other cardiac glycoside drugs can cause asystole or fibrillation of the ventricles of the heart; the use of aminoglycosides kanamycin, gentamicin, neomycin against the background of streptomycin leads to damage to the VIII pair of cranial nerves, irreversible hearing loss, and sometimes to the development of renal failure (relative incompatibility, similar to the effect of an overdose).

Pharmacokinetic incompatibility occurs due to the changes that one of the drugs makes to the conditions of absorption, excretion or circulation in the body of the other drug(s).

The administration of diuretic nephron loops (furosemide, uregit) has a negative effect on aminoglycoside therapy: their concentration in the blood and tissues decreases more quickly, and the nephrotoxic effect increases. On the contrary, streptomycin, disrupting the mechanism of penicillin secretion by the tubular epithelium, extends the period of its therapeutic concentration in the blood (favorable pharmacokinetic potentiation).

There is also a metabolic (always dose-dependent, relative) incompatibility of drugs, which was studied using the example of the combined use of phenobarbital and anticoagulants: phenobarbital promotes accelerated metabolism of the latter and a sharp weakening of their effect.

Table 4. Incompatible drug combinations

In other cases, metabolic incompatibility is based on inhibition of the processes of destruction of the drug substance, decreased clearance, increased concentration in the blood plasma, accompanied by the development of signs of overdose. Thus, monoamine oxidase inhibitors (iprazide, nylamide) inhibit the metabolism of catecholamines. tyramine, serotonin, causing hypertensive reactions.

Classification of antibacterial agents (according to Manten - Wisse)

The problem of combined antibacterial therapy has become more acute. Tens of thousands of antibiotics, differing in their medicinal characteristics, have been obtained, including semisynthetically. Indications for combined antimicrobial therapy are determined by many considerations:

1) the possibility of increasing therapeutic effectiveness;

2) expansion of the spectrum of antibacterial action for an unspecified pathogen;

3) reduction of side effects compared to adequate monotherapy;

4) reducing the risk of the emergence of resistant strains of microbes.

However, when two or more drugs are used simultaneously, four forms of interaction are possible: indifference, cumulative effect, potentiation and antagonism.

The difference is that one drug does not have a clear effect on the antibacterial effect of the other.

A cumulative (or additive) effect occurs when the result is the sum of the monotherapeutic effects. If the degree of antibacterial activity of a combination of drugs is greater than the total effect of the components, they speak of potentiation (or synergism). But often the effect of complex use of antibiotics turns out to be less than that of one of the ingredients: antagonism of the action of the drugs occurs. The simultaneous use of antibiotics, between which antagonism is possible, is a direct mistake of the doctor.

Already in the 50s, the principle of combining antibiotics was formulated depending on the type of their effect on the pathogen - bactericidal or bacteriostatic (see classification). When combining antibiotics that have a bactericidal effect, as a rule, a synergistic or additive effect is achieved. The combination of bacteriostatic antibiotics leads to an additive effect or “indifferentiation”.

The combination of bactericidal antibiotics with bacteriostatic drugs is most often undesirable. Mortality from meningococcal sepsis in children when attempting to use penicillin and chloramphenicol simultaneously increased compared with the results obtained when treating one or the other of these drugs separately.

If the microorganism is more sensitive to a component with a bacteriostatic effect, synergism may occur, but when it is sensitive to a bactericidal action, antagonism usually occurs, the bacteriostatic drug reducing the effectiveness of the bactericidal one. Both in venereology and in the treatment of acute pneumonia, the simultaneous use of sulfonamides and penicillin was accompanied by unfavorable results compared with the effect obtained with vigorous treatment with penicillins alone: ​​the “terminating” effect when using a bactericidal antibiotic (abortive course of pneumonia with early administration of penicillin) does not occur .

For monoinfections, combined treatment with antibiotics is rarely justified; for mixed infections, it can be valuable, but only if the conditions for a rational combination of antibiotics are met and all indications and contraindications are taken into account.

To date, it has been established that neither a wide spectrum of antibiotic activity, nor megadoses, nor combinations of antibiotics or sequential replacement of one with another solves the problem of successful treatment of bacterial diseases, as long as this hides an attempt to treat blindly, by trial and error. Precise, targeted, highly targeted treatment is required based on determining the species and individual sensitivity of the pathogen to the therapeutic agent, reliable and timely etiological diagnosis of the disease.

Antibiotics should not be unnecessarily combined with antipyretics, hypnotics, or glucocorticoid drugs (this contradicts the recommendation to use glucocorticoids “under the protection” of antibiotics, which is explained by the priority in some cases of antibacterial therapy, in others - glucocorticoid therapy).

The problem of combined treatment, well studied in antibiotic models, also applies to other areas of chemotherapy for internal diseases. On the one hand, polychemotherapy is becoming increasingly important. It is necessary for oncological diseases and hematological malignancies, where departure from a comprehensive program most often means a violation of the treatment system, failure of drug-induced remission and the death of the patient. A comprehensive approach to the treatment of chronic diseases is being carefully developed. On the other hand, there is a growing need for an increasingly persistent fight against random, arbitrary combinations of pharmacological drugs. The simultaneous use of morphine and anaprilin is considered mortally dangerous, but the consequences depend on the total dose and its adequacy to the patient’s condition. Avoid prescribing anaprilin simultaneously with isoptin (verapamil), anaprilin with monoamine oxidase inhibitors, relaxants while taking quinidine. Miscalculations in the use of drug therapy, despite attempts to individualize it, and often precisely because of uncritical variations, lead to numerous complications.

In the United States, over 10 years (1961-1970), 15 million people were hospitalized due to complications of drug treatment; economic losses exceeded those from infectious diseases.

Nevertheless, the best of complex, multicomponent medicinal prescriptions, not without reason, have become widespread and tested in medical practice. They are characterized by a balance of ingredients, and their “simplification” is not always free of charge. Such drugs include, for example, solutan, theophedrine, antasman used in bronchial asthma, in gastroenterology - vikalin and laxative cocktails, in hepatology - Liv 52 and Essential.

Monotherapy with even the most modern drugs is often only the first stage of treatment. It is then replaced by a more effective, comprehensively calculated complex treatment of the patient. Sometimes this complexity is achieved by including physiotherapeutic and other non-drug treatments, but more often, first of all, we are talking about a combination of pharmacological drugs. Widespread use of a system of stepwise approach to the treatment of patients with progressive forms of arterial hypertension. In place of monotherapy, which at one time was preferred to be carried out with saluretics of the thiazide series, and now varies depending on the characteristics of the process (diuretics with the inclusion of potassium-sparing agents, rauwolfia preparations, beta-blockers, clonidine, calcium antagonists), then comes polytherapy. The process of developing standardized polyingredient recipes is natural. These recipes included depression, developed by A.L. Myasnikov in 1960, and more modern forms - adelfan, brinerdin, triampur, etc.

It is necessary to distinguish between complex drugs that include a set of certain ingredients primarily for the purpose of replenishing a deficiency that occurs in the body or replacement therapy, and the combined use of pharmacodynamically active drugs. The former include infusion solutions of complex electrolyte composition, multivitamin and polyamino acid formulations. The second is complex formulations of synergistically acting drugs. Rational selection of a complex drug in the second case is much more difficult, but prescriptions of the first type also require strict adherence to optimal ratios (Table 5). With maintenance, long-term treatment, the development of tolerance to a particular drug and a decrease in its effectiveness become important. Along with other methods of overcoming this phenomenon (intermittent course, rhythm of techniques), the correct use of polytherapy is of great importance.

Table 5. Pharmacological incompatibility of vitamins during long-term administration in high doses[I. B. Maksimovich, E. A. Lvgeda]

To carry out maintenance therapy, special dosage forms are created that meet a number of conditions, including complex ones that have a sufficient duration of action, allowing one tablet to be taken during the day. Sometimes multi-ingredient tablets are made multilayer if necessary (Mexaza, Panzinorm).

One of the tasks of creating official complex pharmacological forms is to prevent the arbitrary use of random drug complexes, limited only by direct contraindications. The end result of polypharmacy always differs from the expected sum of the desired effects, since the forms of interaction of these effects in the body are diverse and side effects are difficult to predict.

Increased caution is necessary when treating children, pregnant women, as well as when including intravenous, drip, intramuscular and other parenteral administrations in the complex.

Features of pharmacotherapy in children and the elderly. Until the middle of the 20th century. F.'s features were studied mainly in children, and only in the 60s. Within the framework of age-related pharmacology, a geriatric direction has emerged.

Pharmacotherapy in children has a more complex approach to determining its tactics, because By the nature of interaction with most medications, a child’s body approaches an adult’s body only at 12-14 years of age. The differences in the state of the systems that react with the drug and determine its transport, metabolism and excretion in different periods of the child’s postnatal development are so significant that they exclude any standardization in the tactics of drug therapy in children without taking into account the degree of development of these systems for a given age period.

The peculiarities of the interaction of the body with the drug are most pronounced in newborns and infants. For the bioavailability of drugs in enteral dosage forms, the richness of the circulatory and lymphatic vascularization of the stomach and intestines, the low acidity of gastric juice (3-4 times lower than in adults), and the high permeability of the pores of the intestinal wall for large molecules are essential during these periods. In general, these features facilitate the passive transport of drugs, especially alkaloids (caffeine, etc.), while the bioavailability of drugs that require active transport is reduced in infants (for example, tetracycline, riboflavin, retinol are less absorbed). The amount of albumin in the plasma of newborns and infants is less than in adults, while many drugs are less tightly bound to proteins and are more easily replaced by natural metabolites, such as bilirubin. This creates conditions for increased desorption (release from protein binding) of drugs bound by proteins (digoxin, sulfonamides, etc.) and an increase in the free fraction of the drug in the blood with a corresponding increase in action up to toxic, which is especially important to consider in cases of hyperbilirubinemia in newborns and with the combined use of drugs that are competitively bound by plasma proteins. Some drugs are eliminated from the blood more slowly the younger the child. Thus, the half-life of sibazon from the blood in premature newborns is 2 times longer than in full-term newborns, and 4 times longer than in children 4-8 years old.

The distribution of drugs in a child’s body follows the same patterns as in an adult, but the penetration of most of them into various organs, including the brain, is higher in newborns and infants than in older children, due to the incomplete development of histohematological barriers. This is due, in particular, to the increased intake of various fat-soluble drugs into the brain, incl. a number of sleeping pills, the inhibitory effect of which on the brain of newborns is more pronounced than in adults. At the same time, many of these drugs are less absorbed by brain tissue, because in newborns it contains less lipids. The peculiarities of the kinetics of water-soluble drugs are determined by the large volume of extracellular water in the body of newborns and infants, as well as the high rate of exchange of extracellular water (almost 4 times higher than in adults), which contributes to faster elimination of drugs.

Metabolic inactivation of drugs in children is limited due to the smaller mass of the liver parenchyma, low activity of oxidative enzymes and the detoxification system through the formation of conjugates with glucuronic acid, which completes its formation only by the age of 12. In newborns, qualitative differences have also been established in the biotransformation of a number of drugs (for example, aminazine, sibazon, promedol), characterized by the formation of metabolites that are not detected in older children and adults. The abundance of exceptions to the patterns established in adults requires knowledge of the characteristics of the biotransformation of individual drugs. It is known, for example, that in newborns and infants the metabolism of amidopyrine, butadione, sibazon, chloramphenicol, morphine and a number of other drugs is significantly slowed down. The position according to which in children the rate of metabolism of drugs, resulting in the formation of conjugates with sulfuric acid, does not differ significantly from that in adults, and for drugs inactivated as a result of the formation of conjugates with glucuronic acid, the metabolism is slower, the less child's age.

The excretion of drugs by the kidneys in newborns and children of the first year of life is generally slowed down both due to lower glomerular filtration than in adults (by creatinine excretion - approximately 2 times) and lower permeability of the basement membrane of the renal glomeruli, and due to the incomplete development of enzyme enzymes. systems that ensure excretion of drugs and their metabolites in the renal tubules. Some drugs, such as benzylpenicillin, are used in children as early as 2-3 months of age. excreted at the same rate as in adults.

When choosing a drug, in addition to the characteristics of its pharmacokinetics in children, the characteristics of its pharmacodynamics are also taken into account, which depend on the level of development of the systems that determine the implementation of the pharmacological effect at a given age of the child. For example, the hypotensive effect of ganglion blockers in children of the first two years of life is weak, in infants the hypertensive effect of ephedrine is weakened with a pronounced effect on blood pressure of mezatone, etc. The therapeutic significance of the expected pharmacological effect is correlated with the risk of undesirable effects of the drug, the likelihood and nature of which are not the same in children of different ages and in adults. For example, compared with older children, children of the first 3 months. life, the likelihood of developing hemolysis and methemoglobinemia due to the use of nitrofurans, vikasol and other drugs is much higher, which is due to the high content of fetal hemoglobin in their blood. The probability of toxic effects of drugs in equivalent (per unit body weight) doses in newborns and infants is lower for some drugs (adrenaline, strychnine), for others it is higher (morphine, chloramphenicol, tetracycline, etc.). Taking into account the undesirable effects of drugs I.V. Markov and V.I. Kalinicheva (1980) distinguishes groups of drugs, the use of which in newborns is no more dangerous than in other age groups (penicillins, macrolides, nystatin, caffeine, phenobarbital, etc.); drugs used with caution (atropine, aminazine, amidopyrine, cardiac glycosides, aminophylline, gentamicin, lincomycin); drugs contraindicated in newborns (chloramphenicol, tetracycline, kanamycin, monomycin, nalidixic acid, sulfonamides, salicylates, morphine and morphine-like analgesics).

Determining the dose of a drug in children cannot be limited to the search for criteria for equivalence to the dose of an adult (in terms of body weight, body surface, etc.), since the metabolism and excretion of drugs in children may differ qualitatively from those of adults. Average doses of drugs are determined from clinical experience of their use in different age groups of children. Based on this experience, general dosage patterns are established in units of mass (grams, milligrams), volume (drops, milliliters), activity per 1 kg of body weight or 1 m2 of body surface or per 1 month or 1 year of a child’s life for certain drugs (anaprilin , aminophylline, etc.), and in more complex expressions - in milligrams per 1 kg of body weight for certain age periods (taking into account age-related changes in drug metabolism systems and the reactivity of the child’s body).

The choice of effect criteria and means of monitoring drug action in children in all age groups is limited mainly by objective signs of the dynamics of the pathological process, syndrome or symptom, because subjective criteria (informativeness of the patient’s complaints) are much less valuable than in adults, and in children of the first year of life they are completely absent. The use of objective instrumental monitoring tools that require the patient’s active participation in the study (a certain posture, arbitrary holding or increased breathing, etc.) is also limited. All this creates difficulties in ensuring controlled exercise, especially in young children. Accordingly, the importance of continuous clinical monitoring of the slightest deviations in the state of various functions and behavior of the child during the use of the drug increases, especially during the expected periods of its pharmacological action.

The withdrawal of medications in children is carried out on the same grounds as in adults.

Pharmacotherapy in elderly and senile people acquires features as the metabolism, barrier functions of tissues, metabolic and drug excretion systems undergo changes during the aging of the body, as well as sensitivity to drugs of various organs and the reactivity of the body as a whole. Insufficient caution in the selection and dosage of medications for elderly patients is, apparently, one of the reasons for the higher frequency of side effects in them (according to various researchers, in people over 70 years of age, side effects of medications are observed 3-7 times more often, than in patients 20-30 years old).

The bioavailability of drugs administered enterally in old age decreases due to a decrease in the secretory, motor and absorption functions of the gastrointestinal tract. The distribution of drugs is affected by the decrease in water content in the body and the amount of albumin in the blood, which is characteristic of elderly and senile people, a decrease in the weight of most organs, the number of functioning blood vessels and a narrowing of their lumen, and a change in the permeability of histohematic barriers. The mass of the liver parenchyma in people over 70 years of age is reduced, the antitoxic function of the liver is reduced, and the activity of oxidative enzymes is weakened. This is associated with a slowdown in the metabolism of drugs, in particular those whose inactivation ends with the formation of sulfates. The rate of excretion of drugs by the kidneys is also reduced due to a weakening of energy-dependent excretion through the tubular epithelium, a decrease in the number of functioning nephrons (in persons over 70 years of age there are 30-50% fewer of them), a decrease in the efficiency of renal plasma flow and glomerular filtration rate.

F.'s tactics in elderly and senile people should include: limiting the choice of drugs to low-toxic ones: prescribing higher doses during the initial use of drugs in enteral dosage forms; reducing the dose of drugs (especially when administered parenterally) excreted by the kidneys or slowly metabolized in the liver. Doses of some medications (neuroleptics, cardiotonics, diuretics, etc.) recommended for the elderly and senile for initial use average 1/2 the dose of a middle-aged adult. However, these provisions do not apply to all drugs (for example, vitamins, many antibiotics and sulfonamides can be used in normal doses), therefore, in order to develop rational pharmacotherapy tactics, one should take into account the uniqueness of pharmacological effects, which in elderly and senile people is determined by changes in sensitivity to certain medications and even qualitative changes in reactions to individual drugs.

In elderly and senile people, regular features of reactions to drugs acting on the central nervous system have been established, which is associated, in particular, with an increase in dystrophic changes in neurons as the body ages, with a decrease in the number of nerve cells and the number of axons, and also with a decrease in the functional activity of the central nervous system. It has been shown that for the manifestation of an exciting effect on the central nervous system. phenamine, strychnine, ephedrine, older people require larger doses of these drugs than middle-aged people. To drugs that depress the central nervous system, in particular to barbiturates and other hypnotics. on the contrary, increased sensitivity is noted to neuroleptics of various groups, including reserpine, narcotic analgesics, some benzodiazepine derivatives (chlozepid), etc. The direct pharmacological effect of these drugs is achieved in smaller doses and is often combined with pronounced manifestations of undesirable effects (respiratory depression, muscle relaxation, stimulation of the vomiting center), while the use of these drugs in doses that are therapeutic for middle-aged people often leads to intoxication. Thus, special care should be taken when using even low-toxic hypnotics and sedatives (for example, bromide poisoning), especially neuroleptics, in elderly people.

In elderly people, more often than in other age groups, there is a need to use cardiotonic, antihypertensive and diuretic drugs. Clinical observations indicate increased sensitivity of the myocardium of elderly people to the toxic effects of cardiac glycosides. This makes it preferable to choose low-accumulating drugs, slow the pace of initial digitalization and requires more frequent monitoring of the adequacy of the selected dose. When choosing antihypertensive drugs, take into account the increased risk of a sharp decrease in blood pressure and protostatic collapse when using ganglion blockers, sympatholytics, as well as undesirable effects on the central nervous system. a number of drugs (reserpine, dehydralazine). Under the influence of saluretics, elderly people may experience a more pronounced loss of potassium (per unit volume of diuresis) with worse tolerance to these losses and the ability to restore electrolyte balance than middle-aged people. At the same time, there is often increased sensitivity to the action of aldosterone antagonists, as a result of which they can be used in lower doses.

There is reason to believe that the simultaneous use of vitamin complexes, in particular vitamins B1, B6, B15, contributes to increasing the effectiveness and reducing the undesirable consequences of F. in the elderly and senile.

Features of pharmacotherapy in pregnant women and nursing mothers. Prevention of undesirable effects on the fetus and on the infant of drugs that penetrate the placenta or are excreted in mother's milk is central to F.'s tactics in pregnant women and nursing mothers.

Features of pharmacotherapy in pregnant women are largely determined by the prognosis of the effect of the drug on the developing fetus. The placental barrier is permeable to varying degrees for the vast majority of drugs. Getting into the blood and tissues of the fetus, the drug can cause: a pharmacological effect; embryotoxic effect, fetal development disorder, teratogenic effect.

The pharmacological effect in the fetus, depending on the dose of the drug, may differ significantly from that observed in a pregnant woman. Thus, prescribing indirect anticoagulants to a pregnant woman in doses that cause a moderate decrease in prothrombin in her can cause multiple hemorrhages in the tissues of the fetus. The quantitative and qualitative features of the pharmacological effect in the fetus are determined by the imperfect development of its systems that interact with drugs, the characteristics of their distribution in tissues (for example, 3 times more mesatone accumulates in the fetal brain than in a pregnant woman), metabolism and excretion.

The embryotoxic effect is most characteristic of drugs that are inactivated by their metabolism, because The enzyme activity of liver microsomes in the fetus is low. Imperfect metabolism explains the high toxicity to the fetus of chloramphenicol, morphine, short-acting barbiturates (hexenal, sodium thiopental) with less toxicity of long-acting barbiturates (barbital, phenobarbital), which are excreted from the body mainly unchanged. A peculiar form of unusual action of drugs that displace protein-bound bilirubin is the so-called cerebral jaundice. It is observed in the fetus when prescribed to pregnant women for a long time or in high doses of drugs bound by plasma proteins (sulfonamides, sibazone, hydrocortisone, etc.), and is explained by the weakness of the blood-brain barrier in the fetus and the fragile connection of bilirubin with plasma protein.

The indirect effect of drugs on fetal development has different forms. These include, for example, fetal breathing disorders due to decreased placental blood flow or hypoxemia when pregnant women use adrenomimetics that cause vasospasm, drugs that bind hemoglobin (nitrites), drugs that provoke exacerbation of bronchial asthma in a pregnant woman (acetylsalicylic acid, etc.); deficiency of B vitamins when using antibiotics, diuretics, laxatives; calcium deficiency when using tetracycline; hypercortisolism syndrome due to the displacement of cortisol by drugs bound by plasma proteins.

The teratogenic effect of drugs is most pronounced during the so-called critical periods of embryogenesis - the implantation period (the first week after conception), the placentation period (9-12 weeks) and especially during the period of organogenesis (3-6 weeks of pregnancy). From the second trimester of pregnancy, the likelihood of a teratogenic effect of drugs decreases, but is not completely excluded, because subtle processes of functional differentiation of fetal tissues continue. It is believed that the teratogenic effect of some drugs is explained by their ability to be included in the metabolism of the fetus due to the similarity of their chemical structure with natural metabolites (for example, the teratogenic activity of halidomide was associated with its similarity to riboflavin). In animal experiments, fetal development abnormalities are caused by a large number of drugs, but since species differences have also been established, the value of experimental data for predicting the teratogenic effect of individual drugs in humans is not high. Of the drugs that affect the central nervous system, teratogenic activity was found, in addition to thalidomide, in phenothiazine derivatives (cause various developmental anomalies in animals and phocomelia in humans), reserpine, meprotane, chlozepid; The high teratogenic activity of some vitamin preparations has been experimentally established, in particular retinol (cleft palate in 100% of animals, anencephaly in 50%. microphthalmia, absence of a lens are possible), nicotinic acid, as well as benzylpenicillin (syndactyly in 45% of animals), adrenocorticotropic hormone, cortisone , cytostatic agents.

Thus, taking into account the effect of drugs on the fetus, any pharmacotherapy in the first trimester of pregnancy has relative contraindications due to currently incomplete data on the teratogenic activity of drugs. In subsequent periods of pregnancy, there remain contraindications to drugs with embryotoxic effects and disrupting the normal development of the fetus, as well as to drugs that affect labor. F. is carried out during this period only for serious indications, including the occurrence of diseases that themselves disrupt the course of pregnancy and the development of the fetus.

Most often, the need for the use of medications in pregnant women arises in connection with infectious diseases, as well as phlebothrombosis, which often complicates the course of pregnancy, arterial hypertension, and edema. When choosing drugs in these cases, their comparative danger to the fetus during a given period of pregnancy is taken into account.

Of the antibacterial agents in the first trimester of pregnancy, ampicillin, which does not have teratogenic activity, oxacillin, which poorly penetrates the placental barrier, a combination of these drugs (ampiox), and cephalosporins have advantages. However, in high doses, these drugs, like sulfonamides, can cause “cerebral jaundice” in the fetus. Erythromycin penetrates the placental barrier relatively poorly (concentrations in fetal plasma are 5 times less than in maternal plasma). Long-acting sulfonamides are contraindicated in the first trimester of pregnancy, because they have teratogenic activity. During all periods of pregnancy, the use of tetracycline and chloramphenicol, which have a pronounced embryotoxic effect, should be avoided.

The preferred anticoagulant is heparin, which does not cross the placental barrier and is therefore harmless to the fetus. Indirect anticoagulants are contraindicated not only because of the risk of hemorrhages in the fetus, but their use in the first trimester of pregnancy also threatens developmental anomalies.

Antihypertensive drugs and diuretics are often used for toxicosis in the second half of pregnancy, when a teratogenic effect is unlikely. It is preferable to administer methyldopa, less often Octadine, during hypertensive crises intravenously - apressin (40-100 mg) and dichlorothiazide (150-200 mg) in the form of single infusions (it should be remembered that long-term use of dichlorothiazide causes the development of hyperglycemia, hyperbilirubinemia, thrombocytopenia in the fetus). Reserpine, the biotransformation of which is slow even in a newborn, in a daily dose for a pregnant woman of more than 0.5 mg can cause hypersecretion in the nose and bronchi of the fetus and, as a result, obstruction of the respiratory tract. The use of ganglion blockers is avoided due to the risk of meconium ileus in the fetus.

Of the diuretics, furosemide has teratogenic activity, but in the second half of pregnancy its use is practically not limited. When using dichlorothiazide in pregnant women with preeclampsia, take into account the possibility of an increase in the level of uric acid in the blood.

Features of pharmacotherapy in nursing mothers are reduced to reducing the risk of unwanted effects of drugs taken by the mother on the infant. Drugs used for washing nipples enter the child's body during feeding and can have a toxic effect, in particular solutions of boric acid (cumulate in the child's tissues, leading to metabolic acidosis and kidney damage) and lead acetate (threat of lead intoxication with the development of encephalopathy). Women using such solutions should thoroughly wash their nipples with water before feeding their baby.

The secretion of different drugs by the mammary gland varies; the concentration of some of them (for example, thiouracil) in breast milk can be several times higher than in the mother’s blood plasma, which can cause both pharmacological effects and toxic effects on the child’s body. Even a small amount of drugs that pass into breast milk is not always safe, both in terms of toxic effects (due to imperfect metabolism of drugs in the infant’s body) and due to possible sensitization of the child’s body with the formation of drug allergies (Drug allergy).

Lithium salts, thiouracil, nalidixic acid, amantadine, gold preparations, radioactive calcium preparations, iodine are contraindicated for nursing mothers. The younger the infant’s age, the more contraindicated the mother’s treatment with isoniazid (impairs the absorption of vitamin B6), chloramphenicol (toxic effect), tetracyclines (impaired development of the child’s teeth and skeleton); Sulfonamides and salicylates should be used with caution. If a nursing mother needs to use these drugs for a long time or in high doses, it is advisable to transfer the child to artificial feeding.

In drug treatment, combinations of drugs are often used to enhance the effect of one drug with another, limit the dose of each of them, and reduce side effects; for polysyndromic manifestations of the disease - to influence a number of pathogenesis mechanisms, correct changes that have occurred, and alleviate all existing complaints; in the presence of several diseases - for simultaneous treatment of each of them. Since the side effects characteristic of certain medications are known, it is possible to prevent these undesirable consequences of treatment by prescribing protective drugs: treatment with glucocorticoids should be carried out under the protection of antibiotics, antacids, and anabolic agents; Due to the risk of developing dysbiosis, antimicrobial antibiotics should be combined with nystatin or other antifungal drugs. The successes of differentiated pharmacotherapy are increasingly increasing the list of possible and desirable areas of treatment. But therapeutic activity threatens to turn into polypharmacy with its many dangers, the most obvious of which is drug incompatibility.

There are three types of incompatibility of medicinal prescriptions: physical (or physicochemical), chemical and pharmacological. Physical incompatibilities include those that depend on different degrees of solubility of drugs, coagulation of colloidal systems and separation of emulsions, dampening and melting of powders, adsorption phenomena (Table 3).

Table 3. Formation of sediment when combining alkaloid drugs (in 1% solution) with other medicinal substances [Muravyov I. A., Kozmin V. D., Kudrin A. N., 1978]

Chemical incompatibility arises as a result of reactions that occur when solutions are combined in the same volume. They are prevented by separate administration of drugs.

The options for pharmacological incompatibility caused by the interaction of the effects of drugs when used simultaneously are much more diverse and complex.

Information regarding physical and chemical incompatibility is included in prescription reference books, bulletins, and tables. Prescriptions are controlled when filling out a prescription in pharmacies. However, in everyday practice, due to insufficient awareness of doctors and medical personnel, deviations from approved recommendations are often made with negative consequences for the patient.

When a patient takes several tablets at the same time, not only their pharmacological incompatibility is possible, but also chemical interaction in the gastrointestinal tract in conditions where digestive juices and other ingredients of chyme become biological catalysts for the reactions that occur.

Pharmacological incompatibility has various causes and forms. Antagonistic (or absolute) incompatibility is possible in cases where drugs have multidirectional effects on processes occurring in a cell, tissue, organ or whole organism, and the effect of one is suppressed by the effect of the other. This type of incompatibility is successfully used in the treatment of poisoning when the drug is administered as an antidote: for example, atropine for poisoning with cholinesterase inhibitors, organophosphorus substances, fly agaric (muscarine), pilocarpine; on the contrary, pilocarpine, proserine, physostigmine - in case of atropine poisoning.

Incompatibility also arises between synergists due to the fact that the risk of overdose or increased side effects increases disproportionately. The simultaneous administration of a beta-blocker, digoxin and reserpine causes bradycardia, conduction disturbances, and threatens the development of arrhythmias; administration of strophanthin during treatment with other cardiac glycoside drugs can cause asystole or fibrillation of the ventricles of the heart; the use of aminoglycosides kanamycin, gentamicin, neomycin against the background of streptomycin leads to damage to the VIII pair of cranial nerves, irreversible hearing loss, and sometimes to the development of renal failure (relative incompatibility, similar to the effect of an overdose).

Pharmacokinetic incompatibility occurs due to the changes that one of the drugs makes to the conditions of absorption, excretion or circulation in the body of the other drug(s).

The administration of diuretic nephron loops (furosemide, uregit) has a negative effect on aminoglycoside therapy: their concentration in the blood and tissues decreases more quickly, and the nephrotoxic effect increases. On the contrary, streptomycin, disrupting the mechanism of penicillin secretion by the tubular epithelium, extends the period of its therapeutic concentration in the blood (favorable pharmacokinetic potentiation).

There is also a metabolic (always dose-dependent, relative) incompatibility of drugs, which was studied using the example of the combined use of phenobarbital and anticoagulants: phenobarbital promotes accelerated metabolism of the latter and a sharp weakening of their effect.

Table 4. Incompatible drug combinations

In other cases, metabolic incompatibility is based on inhibition of the processes of destruction of the drug substance, decreased clearance, increased concentration in the blood plasma, accompanied by the development of signs of overdose. Thus, monoamine oxidase inhibitors (iprazide, nylamide) inhibit the metabolism of catecholamines. tyramine, serotonin, causing hypertensive reactions.

Classification of antibacterial agents (according to Manten - Wisse)

The problem of combined antibacterial therapy has become more acute. Tens of thousands of antibiotics, differing in their medicinal characteristics, have been obtained, including semisynthetically. Indications for combined antimicrobial therapy are determined by many considerations:

1) the possibility of increasing therapeutic effectiveness;

2) expansion of the spectrum of antibacterial action for an unspecified pathogen;

3) reduction of side effects compared to adequate monotherapy;

4) reducing the risk of the emergence of resistant strains of microbes.

However, when two or more drugs are used simultaneously, four forms of interaction are possible: indifference, cumulative effect, potentiation and antagonism.

The difference is that one drug does not have a clear effect on the antibacterial effect of the other.

A cumulative (or additive) effect occurs when the result is the sum of the monotherapeutic effects. If the degree of antibacterial activity of a combination of drugs is greater than the total effect of the components, they speak of potentiation (or synergism). But often the effect of complex use of antibiotics turns out to be less than that of one of the ingredients: antagonism of the action of the drugs occurs. The simultaneous use of antibiotics, between which antagonism is possible, is a direct mistake of the doctor.

Already in the 50s, the principle of combining antibiotics was formulated depending on the type of their effect on the pathogen - bactericidal or bacteriostatic (see classification). When combining antibiotics that have a bactericidal effect, as a rule, a synergistic or additive effect is achieved. The combination of bacteriostatic antibiotics leads to an additive effect or “indifferentiation”.

The combination of bactericidal antibiotics with bacteriostatic drugs is most often undesirable. Mortality from meningococcal sepsis in children when attempting to use penicillin and chloramphenicol simultaneously increased compared with the results obtained when treating one or the other of these drugs separately.

If the microorganism is more sensitive to a component with a bacteriostatic effect, synergism may occur, but when it is sensitive to a bactericidal action, antagonism usually occurs, the bacteriostatic drug reducing the effectiveness of the bactericidal one. Both in venereology and in the treatment of acute pneumonia, the simultaneous use of sulfonamides and penicillin was accompanied by unfavorable results compared with the effect obtained with vigorous treatment with penicillins alone: ​​the “terminating” effect when using a bactericidal antibiotic (abortive course of pneumonia with early administration of penicillin) does not occur .

For monoinfections, combined treatment with antibiotics is rarely justified; for mixed infections, it can be valuable, but only if the conditions for a rational combination of antibiotics are met and all indications and contraindications are taken into account.

To date, it has been established that neither a wide spectrum of antibiotic activity, nor megadoses, nor combinations of antibiotics or sequential replacement of one with another solves the problem of successful treatment of bacterial diseases, as long as this hides an attempt to treat blindly, by trial and error. Precise, targeted, highly targeted treatment is required based on determining the species and individual sensitivity of the pathogen to the therapeutic agent, reliable and timely etiological diagnosis of the disease.

Antibiotics should not be unnecessarily combined with antipyretics, hypnotics, or glucocorticoid drugs (this contradicts the recommendation to use glucocorticoids “under the protection” of antibiotics, which is explained by the priority in some cases of antibacterial therapy, in others - glucocorticoid therapy).

The problem of combined treatment, well studied in antibiotic models, also applies to other areas of chemotherapy for internal diseases. On the one hand, polychemotherapy is becoming increasingly important. It is necessary for oncological diseases and hematological malignancies, where departure from a comprehensive program most often means a violation of the treatment system, failure of drug-induced remission and the death of the patient. A comprehensive approach to the treatment of chronic diseases is being carefully developed. On the other hand, there is a growing need for an increasingly persistent fight against random, arbitrary combinations of pharmacological drugs. The simultaneous use of morphine and anaprilin is considered mortally dangerous, but the consequences depend on the total dose and its adequacy to the patient’s condition. Avoid prescribing anaprilin simultaneously with isoptin (verapamil), anaprilin with monoamine oxidase inhibitors, relaxants while taking quinidine. Miscalculations in the use of drug therapy, despite attempts to individualize it, and often precisely because of uncritical variations, lead to numerous complications.

In the United States, over 10 years (1961-1970), 15 million people were hospitalized due to complications of drug treatment; economic losses exceeded those from infectious diseases.

Nevertheless, the best of complex, multicomponent medicinal prescriptions, not without reason, have become widespread and tested in medical practice. They are characterized by a balance of ingredients, and their “simplification” is not always free of charge. Such drugs include, for example, solutan, theophedrine, antasman used in bronchial asthma, in gastroenterology - vikalin and laxative cocktails, in hepatology - Liv 52 and Essential.

Monotherapy with even the most modern drugs is often only the first stage of treatment. It is then replaced by a more effective, comprehensively calculated complex treatment of the patient. Sometimes this complexity is achieved by including physiotherapeutic and other non-drug treatments, but more often, first of all, we are talking about a combination of pharmacological drugs. Widespread use of a system of stepwise approach to the treatment of patients with progressive forms of arterial hypertension. In place of monotherapy, which at one time was preferred to be carried out with saluretics of the thiazide series, and now varies depending on the characteristics of the process (diuretics with the inclusion of potassium-sparing agents, rauwolfia preparations, beta-blockers, clonidine, calcium antagonists), then comes polytherapy. The process of developing standardized polyingredient recipes is natural. These recipes included depression, developed by A.L. Myasnikov in 1960, and more modern forms - adelfan, brinerdin, triampur, etc.

It is necessary to distinguish between complex drugs that include a set of certain ingredients primarily for the purpose of replenishing a deficiency that occurs in the body or replacement therapy, and the combined use of pharmacodynamically active drugs. The former include infusion solutions of complex electrolyte composition, multivitamin and polyamino acid formulations. The second is complex formulations of synergistically acting drugs. Rational selection of a complex drug in the second case is much more difficult, but prescriptions of the first type also require strict adherence to optimal ratios (Table 5). With maintenance, long-term treatment, the development of tolerance to a particular drug and a decrease in its effectiveness become important. Along with other methods of overcoming this phenomenon (intermittent course, rhythm of techniques), the correct use of polytherapy is of great importance.

Table 5. Pharmacological incompatibility of vitamins during long-term administration in high doses[I. B. Maksimovich, E. A. Lvgeda]

To carry out maintenance therapy, special dosage forms are created that meet a number of conditions, including complex ones that have a sufficient duration of action, allowing one tablet to be taken during the day. Sometimes multi-ingredient tablets are made multilayer if necessary (Mexaza, Panzinorm).

One of the tasks of creating official complex pharmacological forms is to prevent the arbitrary use of random drug complexes, limited only by direct contraindications. The end result of polypharmacy always differs from the expected sum of the desired effects, since the forms of interaction of these effects in the body are diverse and side effects are difficult to predict.

Increased caution is necessary when treating children, pregnant women, as well as when including intravenous, drip, intramuscular and other parenteral administrations in the complex.

Features of pharmacotherapy in children and the elderly. Until the middle of the 20th century. F.'s features were studied mainly in children, and only in the 60s. Within the framework of age-related pharmacology, a geriatric direction has emerged.

Pharmacotherapy in children has a more complex approach to determining its tactics, because By the nature of interaction with most medications, a child’s body approaches an adult’s body only at 12-14 years of age. The differences in the state of the systems that react with the drug and determine its transport, metabolism and excretion in different periods of the child’s postnatal development are so significant that they exclude any standardization in the tactics of drug therapy in children without taking into account the degree of development of these systems for a given age period.

The peculiarities of the interaction of the body with the drug are most pronounced in newborns and infants. For the bioavailability of drugs in enteral dosage forms, the richness of the circulatory and lymphatic vascularization of the stomach and intestines, the low acidity of gastric juice (3-4 times lower than in adults), and the high permeability of the pores of the intestinal wall for large molecules are essential during these periods. In general, these features facilitate the passive transport of drugs, especially alkaloids (caffeine, etc.), while the bioavailability of drugs that require active transport is reduced in infants (for example, tetracycline, riboflavin, retinol are less absorbed). The amount of albumin in the plasma of newborns and infants is less than in adults, while many drugs are less tightly bound to proteins and are more easily replaced by natural metabolites, such as bilirubin. This creates conditions for increased desorption (release from protein binding) of drugs bound by proteins (digoxin, sulfonamides, etc.) and an increase in the free fraction of the drug in the blood with a corresponding increase in action up to toxic, which is especially important to consider in cases of hyperbilirubinemia in newborns and with the combined use of drugs that are competitively bound by plasma proteins. Some drugs are eliminated from the blood more slowly the younger the child. Thus, the half-life of sibazon from the blood in premature newborns is 2 times longer than in full-term newborns, and 4 times longer than in children 4-8 years old.

The distribution of drugs in a child’s body follows the same patterns as in an adult, but the penetration of most of them into various organs, including the brain, is higher in newborns and infants than in older children, due to the incomplete development of histohematological barriers. This is due, in particular, to the increased intake of various fat-soluble drugs into the brain, incl. a number of sleeping pills, the inhibitory effect of which on the brain of newborns is more pronounced than in adults. At the same time, many of these drugs are less absorbed by brain tissue, because in newborns it contains less lipids. The peculiarities of the kinetics of water-soluble drugs are determined by the large volume of extracellular water in the body of newborns and infants, as well as the high rate of exchange of extracellular water (almost 4 times higher than in adults), which contributes to faster elimination of drugs.

Metabolic inactivation of drugs in children is limited due to the smaller mass of the liver parenchyma, low activity of oxidative enzymes and the detoxification system through the formation of conjugates with glucuronic acid, which completes its formation only by the age of 12. In newborns, qualitative differences have also been established in the biotransformation of a number of drugs (for example, aminazine, sibazon, promedol), characterized by the formation of metabolites that are not detected in older children and adults. The abundance of exceptions to the patterns established in adults requires knowledge of the characteristics of the biotransformation of individual drugs. It is known, for example, that in newborns and infants the metabolism of amidopyrine, butadione, sibazon, chloramphenicol, morphine and a number of other drugs is significantly slowed down. The position according to which in children the rate of metabolism of drugs, resulting in the formation of conjugates with sulfuric acid, does not differ significantly from that in adults, and for drugs inactivated as a result of the formation of conjugates with glucuronic acid, the metabolism is slower, the less child's age.

The excretion of drugs by the kidneys in newborns and children of the first year of life is generally slowed down both due to lower glomerular filtration than in adults (by creatinine excretion - approximately 2 times) and lower permeability of the basement membrane of the renal glomeruli, and due to the incomplete development of enzyme enzymes. systems that ensure excretion of drugs and their metabolites in the renal tubules. Some drugs, such as benzylpenicillin, are used in children as early as 2-3 months of age. excreted at the same rate as in adults.

When choosing a drug, in addition to the characteristics of its pharmacokinetics in children, the characteristics of its pharmacodynamics are also taken into account, which depend on the level of development of the systems that determine the implementation of the pharmacological effect at a given age of the child. For example, the hypotensive effect of ganglion blockers in children of the first two years of life is weak, in infants the hypertensive effect of ephedrine is weakened with a pronounced effect on blood pressure of mezatone, etc. The therapeutic significance of the expected pharmacological effect is correlated with the risk of undesirable effects of the drug, the likelihood and nature of which are not the same in children of different ages and in adults. For example, compared with older children, children of the first 3 months. life, the likelihood of developing hemolysis and methemoglobinemia due to the use of nitrofurans, vikasol and other drugs is much higher, which is due to the high content of fetal hemoglobin in their blood. The probability of toxic effects of drugs in equivalent (per unit body weight) doses in newborns and infants is lower for some drugs (adrenaline, strychnine), for others it is higher (morphine, chloramphenicol, tetracycline, etc.). Taking into account the undesirable effects of drugs I.V. Markov and V.I. Kalinicheva (1980) distinguishes groups of drugs, the use of which in newborns is no more dangerous than in other age groups (penicillins, macrolides, nystatin, caffeine, phenobarbital, etc.); drugs used with caution (atropine, aminazine, amidopyrine, cardiac glycosides, aminophylline, gentamicin, lincomycin); drugs contraindicated in newborns (chloramphenicol, tetracycline, kanamycin, monomycin, nalidixic acid, sulfonamides, salicylates, morphine and morphine-like analgesics).

Determining the dose of a drug in children cannot be limited to the search for criteria for equivalence to the dose of an adult (in terms of body weight, body surface, etc.), since the metabolism and excretion of drugs in children may differ qualitatively from those of adults. Average doses of drugs are determined from clinical experience of their use in different age groups of children. Based on this experience, general dosage patterns are established in units of mass (grams, milligrams), volume (drops, milliliters), activity per 1 kg of body weight or 1 m2 of body surface or per 1 month or 1 year of a child’s life for certain drugs (anaprilin , aminophylline, etc.), and in more complex expressions - in milligrams per 1 kg of body weight for certain age periods (taking into account age-related changes in drug metabolism systems and the reactivity of the child’s body).

The choice of effect criteria and means of monitoring drug action in children in all age groups is limited mainly by objective signs of the dynamics of the pathological process, syndrome or symptom, because subjective criteria (informativeness of the patient’s complaints) are much less valuable than in adults, and in children of the first year of life they are completely absent. The use of objective instrumental monitoring tools that require the patient’s active participation in the study (a certain posture, arbitrary holding or increased breathing, etc.) is also limited. All this creates difficulties in ensuring controlled exercise, especially in young children. Accordingly, the importance of continuous clinical monitoring of the slightest deviations in the state of various functions and behavior of the child during the use of the drug increases, especially during the expected periods of its pharmacological action.

The withdrawal of medications in children is carried out on the same grounds as in adults.

Pharmacotherapy in elderly and senile people acquires features as the metabolism, barrier functions of tissues, metabolic and drug excretion systems undergo changes during the aging of the body, as well as sensitivity to drugs of various organs and the reactivity of the body as a whole. Insufficient caution in the selection and dosage of medications for elderly patients is, apparently, one of the reasons for the higher frequency of side effects in them (according to various researchers, in people over 70 years of age, side effects of medications are observed 3-7 times more often, than in patients 20-30 years old).

The bioavailability of drugs administered enterally in old age decreases due to a decrease in the secretory, motor and absorption functions of the gastrointestinal tract. The distribution of drugs is affected by the decrease in water content in the body and the amount of albumin in the blood, which is characteristic of elderly and senile people, a decrease in the weight of most organs, the number of functioning blood vessels and a narrowing of their lumen, and a change in the permeability of histohematic barriers. The mass of the liver parenchyma in people over 70 years of age is reduced, the antitoxic function of the liver is reduced, and the activity of oxidative enzymes is weakened. This is associated with a slowdown in the metabolism of drugs, in particular those whose inactivation ends with the formation of sulfates. The rate of excretion of drugs by the kidneys is also reduced due to a weakening of energy-dependent excretion through the tubular epithelium, a decrease in the number of functioning nephrons (in persons over 70 years of age there are 30-50% fewer of them), a decrease in the efficiency of renal plasma flow and glomerular filtration rate.

F.'s tactics in elderly and senile people should include: limiting the choice of drugs to low-toxic ones: prescribing higher doses during the initial use of drugs in enteral dosage forms; reducing the dose of drugs (especially when administered parenterally) excreted by the kidneys or slowly metabolized in the liver. Doses of some medications (neuroleptics, cardiotonics, diuretics, etc.) recommended for the elderly and senile for initial use average 1/2 the dose of a middle-aged adult. However, these provisions do not apply to all drugs (for example, vitamins, many antibiotics and sulfonamides can be used in normal doses), therefore, in order to develop rational pharmacotherapy tactics, one should take into account the uniqueness of pharmacological effects, which in elderly and senile people is determined by changes in sensitivity to certain medications and even qualitative changes in reactions to individual drugs.

In elderly and senile people, regular features of reactions to drugs acting on the central nervous system have been established, which is associated, in particular, with an increase in dystrophic changes in neurons as the body ages, with a decrease in the number of nerve cells and the number of axons, and also with a decrease in the functional activity of the central nervous system. It has been shown that for the manifestation of an exciting effect on the central nervous system. phenamine, strychnine, ephedrine, older people require larger doses of these drugs than middle-aged people. To drugs that depress the central nervous system, in particular to barbiturates and other hypnotics. on the contrary, increased sensitivity is noted to neuroleptics of various groups, including reserpine, narcotic analgesics, some benzodiazepine derivatives (chlozepid), etc. The direct pharmacological effect of these drugs is achieved in smaller doses and is often combined with pronounced manifestations of undesirable effects (respiratory depression, muscle relaxation, stimulation of the vomiting center), while the use of these drugs in doses that are therapeutic for middle-aged people often leads to intoxication. Thus, special care should be taken when using even low-toxic hypnotics and sedatives (for example, bromide poisoning), especially neuroleptics, in elderly people.

In elderly people, more often than in other age groups, there is a need to use cardiotonic, antihypertensive and diuretic drugs. Clinical observations indicate increased sensitivity of the myocardium of elderly people to the toxic effects of cardiac glycosides. This makes it preferable to choose low-accumulating drugs, slow the pace of initial digitalization and requires more frequent monitoring of the adequacy of the selected dose. When choosing antihypertensive drugs, take into account the increased risk of a sharp decrease in blood pressure and protostatic collapse when using ganglion blockers, sympatholytics, as well as undesirable effects on the central nervous system. a number of drugs (reserpine, dehydralazine). Under the influence of saluretics, elderly people may experience a more pronounced loss of potassium (per unit volume of diuresis) with worse tolerance to these losses and the ability to restore electrolyte balance than middle-aged people. At the same time, there is often increased sensitivity to the action of aldosterone antagonists, as a result of which they can be used in lower doses.

There is reason to believe that the simultaneous use of vitamin complexes, in particular vitamins B1, B6, B15, contributes to increasing the effectiveness and reducing the undesirable consequences of F. in the elderly and senile.

Features of pharmacotherapy in pregnant women and nursing mothers. Prevention of undesirable effects on the fetus and on the infant of drugs that penetrate the placenta or are excreted in mother's milk is central to F.'s tactics in pregnant women and nursing mothers.

Features of pharmacotherapy in pregnant women are largely determined by the prognosis of the effect of the drug on the developing fetus. The placental barrier is permeable to varying degrees for the vast majority of drugs. Getting into the blood and tissues of the fetus, the drug can cause: a pharmacological effect; embryotoxic effect, fetal development disorder, teratogenic effect.

The pharmacological effect in the fetus, depending on the dose of the drug, may differ significantly from that observed in a pregnant woman. Thus, prescribing indirect anticoagulants to a pregnant woman in doses that cause a moderate decrease in prothrombin in her can cause multiple hemorrhages in the tissues of the fetus. The quantitative and qualitative features of the pharmacological effect in the fetus are determined by the imperfect development of its systems that interact with drugs, the characteristics of their distribution in tissues (for example, 3 times more mesatone accumulates in the fetal brain than in a pregnant woman), metabolism and excretion.

The embryotoxic effect is most characteristic of drugs that are inactivated by their metabolism, because The enzyme activity of liver microsomes in the fetus is low. Imperfect metabolism explains the high toxicity to the fetus of chloramphenicol, morphine, short-acting barbiturates (hexenal, sodium thiopental) with less toxicity of long-acting barbiturates (barbital, phenobarbital), which are excreted from the body mainly unchanged. A peculiar form of unusual action of drugs that displace protein-bound bilirubin is the so-called cerebral jaundice. It is observed in the fetus when prescribed to pregnant women for a long time or in high doses of drugs bound by plasma proteins (sulfonamides, sibazone, hydrocortisone, etc.), and is explained by the weakness of the blood-brain barrier in the fetus and the fragile connection of bilirubin with plasma protein.

The indirect effect of drugs on fetal development has different forms. These include, for example, fetal breathing disorders due to decreased placental blood flow or hypoxemia when pregnant women use adrenomimetics that cause vasospasm, drugs that bind hemoglobin (nitrites), drugs that provoke exacerbation of bronchial asthma in a pregnant woman (acetylsalicylic acid, etc.); deficiency of B vitamins when using antibiotics, diuretics, laxatives; calcium deficiency when using tetracycline; hypercortisolism syndrome due to the displacement of cortisol by drugs bound by plasma proteins.

The teratogenic effect of drugs is most pronounced during the so-called critical periods of embryogenesis - the implantation period (the first week after conception), the placentation period (9-12 weeks) and especially during the period of organogenesis (3-6 weeks of pregnancy). From the second trimester of pregnancy, the likelihood of a teratogenic effect of drugs decreases, but is not completely excluded, because subtle processes of functional differentiation of fetal tissues continue. It is believed that the teratogenic effect of some drugs is explained by their ability to be included in the metabolism of the fetus due to the similarity of their chemical structure with natural metabolites (for example, the teratogenic activity of halidomide was associated with its similarity to riboflavin). In animal experiments, fetal development abnormalities are caused by a large number of drugs, but since species differences have also been established, the value of experimental data for predicting the teratogenic effect of individual drugs in humans is not high. Of the drugs that affect the central nervous system, teratogenic activity was found, in addition to thalidomide, in phenothiazine derivatives (cause various developmental anomalies in animals and phocomelia in humans), reserpine, meprotane, chlozepid; The high teratogenic activity of some vitamin preparations has been experimentally established, in particular retinol (cleft palate in 100% of animals, anencephaly in 50%. microphthalmia, absence of a lens are possible), nicotinic acid, as well as benzylpenicillin (syndactyly in 45% of animals), adrenocorticotropic hormone, cortisone , cytostatic agents.

Thus, taking into account the effect of drugs on the fetus, any pharmacotherapy in the first trimester of pregnancy has relative contraindications due to currently incomplete data on the teratogenic activity of drugs. In subsequent periods of pregnancy, there remain contraindications to drugs with embryotoxic effects and disrupting the normal development of the fetus, as well as to drugs that affect labor. F. is carried out during this period only for serious indications, including the occurrence of diseases that themselves disrupt the course of pregnancy and the development of the fetus.

Most often, the need for the use of medications in pregnant women arises in connection with infectious diseases, as well as phlebothrombosis, which often complicates the course of pregnancy, arterial hypertension, and edema. When choosing drugs in these cases, their comparative danger to the fetus during a given period of pregnancy is taken into account.

Of the antibacterial agents in the first trimester of pregnancy, ampicillin, which does not have teratogenic activity, oxacillin, which poorly penetrates the placental barrier, a combination of these drugs (ampiox), and cephalosporins have advantages. However, in high doses, these drugs, like sulfonamides, can cause “cerebral jaundice” in the fetus. Erythromycin penetrates the placental barrier relatively poorly (concentrations in fetal plasma are 5 times less than in maternal plasma). Long-acting sulfonamides are contraindicated in the first trimester of pregnancy, because they have teratogenic activity. During all periods of pregnancy, the use of tetracycline and chloramphenicol, which have a pronounced embryotoxic effect, should be avoided.

The preferred anticoagulant is heparin, which does not cross the placental barrier and is therefore harmless to the fetus. Indirect anticoagulants are contraindicated not only because of the risk of hemorrhages in the fetus, but their use in the first trimester of pregnancy also threatens developmental anomalies.

Antihypertensive drugs and diuretics are often used for toxicosis in the second half of pregnancy, when a teratogenic effect is unlikely. It is preferable to administer methyldopa, less often Octadine, during hypertensive crises intravenously - apressin (40-100 mg) and dichlorothiazide (150-200 mg) in the form of single infusions (it should be remembered that long-term use of dichlorothiazide causes the development of hyperglycemia, hyperbilirubinemia, thrombocytopenia in the fetus). Reserpine, the biotransformation of which is slow even in a newborn, in a daily dose for a pregnant woman of more than 0.5 mg can cause hypersecretion in the nose and bronchi of the fetus and, as a result, obstruction of the respiratory tract. The use of ganglion blockers is avoided due to the risk of meconium ileus in the fetus.

Of the diuretics, furosemide has teratogenic activity, but in the second half of pregnancy its use is practically not limited. When using dichlorothiazide in pregnant women with preeclampsia, take into account the possibility of an increase in the level of uric acid in the blood.

Features of pharmacotherapy in nursing mothers are reduced to reducing the risk of unwanted effects of drugs taken by the mother on the infant. Drugs used for washing nipples enter the child's body during feeding and can have a toxic effect, in particular solutions of boric acid (cumulate in the child's tissues, leading to metabolic acidosis and kidney damage) and lead acetate (threat of lead intoxication with the development of encephalopathy). Women using such solutions should thoroughly wash their nipples with water before feeding their baby.

The secretion of different drugs by the mammary gland varies; the concentration of some of them (for example, thiouracil) in breast milk can be several times higher than in the mother’s blood plasma, which can cause both pharmacological effects and toxic effects on the child’s body. Even a small amount of drugs that pass into breast milk is not always safe, both in terms of toxic effects (due to imperfect metabolism of drugs in the infant’s body) and due to possible sensitization of the child’s body with the formation of drug allergies (Drug allergy).

Lithium salts, thiouracil, nalidixic acid, amantadine, gold preparations, radioactive calcium preparations, iodine are contraindicated for nursing mothers. The younger the infant’s age, the more contraindicated the mother’s treatment with isoniazid (impairs the absorption of vitamin B6), chloramphenicol (toxic effect), tetracyclines (impaired development of the child’s teeth and skeleton); Sulfonamides and salicylates should be used with caution. If a nursing mother needs to use these drugs for a long time or in high doses, it is advisable to transfer the child to artificial feeding.