More than 100 years ago, Abraham Jacobi, the "Father of American Pediatrics" of our time, wrote: “Pediatrics does not deal with small men and women who require “mechanical dose reduction.” The body's response to pharmaceuticals can be very different from adults due to the immaturity of drug distribution, metabolism and excretion systems. What are the features of metabolic processes in the body of a child? What is important for a pediatrician to know?
What features of the child's body affect the action of drugs?
Children's body is constantly in a state of development of morphological biochemical and physiological structures, which indicates their immaturity during childhood. Therefore, the reaction of the child's body to drugs is special. It is important for a pediatrician to remember that a child's development is a non-linear process in which structural and functional changes may not run in parallel, especially during the first 10 years of life.
So, in small children, the stomach is sufficiently vascularized, the acidity of gastric juice is lower, the permeability of the intestinal pores for the passage of large molecules is increased. There is less albumin in the blood plasma, therefore, in infants, drugs are not so closely bonded to plasma proteins, which undoubtedly leads to an increase in desorption and the presence of a free fraction of the drug in the blood. This explains the simplification of passive transport of drugs, as well as their high bioavailability.
In the neonatal period, genes are activated, which leads to increased activity of enzymes and enzymes, on which protein synthesis in the child's body depends. In the brain, the activity of carbonic anhydrase, cholinesterase increases, the concentration of aminobutyric and glutamic acids increases, which take part in the processes of central inhibition. During the period of adaptation of the newborn, the level of glycine, glucose and fatty acids decreases. Therefore, newborn children have weaker humoral and cellular immunity.
Does the dose of drugs depend on the age in the child's body?
A low level of albumin in the blood plasma of a child's body reduces the effectiveness of all antibiotics, except for cephalosporins. The distribution process has its own characteristics, such as the predominance of extracellular fluid in the child's body, the volume of which decreases by almost 1.5 times over 3 months. But with a decrease in the volume of fluid in the body, the final concentration of water-soluble drugs increases. Therefore, in children, the time to reach peak concentration is slowed down, which contributes to the late onset of the therapeutic effect.
Thus, some drugs that are distributed in a liquid medium (atropine, aminoglycosides) are prescribed to children at a higher dose. With increasing age, the dose of such drugs is reduced. This refutes the common belief that the doses of all drugs should be increased or decreased in the child's body, based on age.
Peculiarities of the process of metabolism of drugs in the child's body
But the processes of metabolism and detoxification of drugs in children are reduced due to the small mass of the liver parenchyma, low activity of oxidative enzymes and the detoxification system. The excretion of drugs by the kidneys in newborns and infants is slowed down, which is associated with lower glomerular filtration and lower permeability of the basement membrane of the renal glomeruli. By the nature of the interaction of the body with most drugs, the child's body begins to work like an adult by the age of 12-14.
In children, compared with adults, the frequency of side effects is increased. At the same time, the younger the child, the more sensitive it is to side effects. Often, side effects are observed with oral administration of drugs due to underdeveloped liver and kidney function, the intensity of metabolic processes. According to the frequency of occurrence of side effects, drugs can be distributed in descending order: antibiotics, analgesics, tranquilizers, glucocorticoids, antiepileptics, cardiac glycosides.
What influences drug metabolism?
The condition that affects the speed, strength and nature of the development of the effect, as well as the metabolic process, is the form of the drug and the route of its administration. Form plays an important role in achieving the effect. Liquid forms have become widely used due to their painless administration, dosage accuracy, uniformity and speed of absorption and excretion.
In pediatrics, oral medications are the mainstay, despite the low effectiveness of some of them. With a reasonable choice, such a technique brings an effect without affecting the metabolic processes.
Against the background of taking syrups, one should take into account the decrease in the effectiveness of drugs, as well as the slowdown in absorption and excretion from the body. This is important to consider if it is necessary to create a high concentration during antibiotic therapy. The rectal route of administration of drugs allows you to achieve the same effect as oral administration.
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