Children are in the growth and development stage, many organs, neurological development is not yet complete, to many drugs are extremely sensitive, so pediatric drug use should be in accordance with the neonatal period, infancy and childhood 3 stages of the correct choice of drugs, reasonable use, in order to ensure drug safety.
I. Characteristics of neonatal medication
Physiological and metabolic processes in the neonatal period are in a stage of rapid development and change, drug metabolism and pharmacokinetic processes are also rapidly changing, so its drug dose can not simply use the adult dose mechanically converted, otherwise the drug will be too much and cause toxic reactions, may also be due to insufficient drug dosage and affect the efficacy.
1, the influence of the route of administration
(1) local drug neonatal body surface area is relatively larger than the adult, the skin keratinization layer is thin, local drug transdermal absorption is fast and more, external application on the skin of infants can cause poisoning drugs such as boric acid, hexachlorophenol, naphthalene, polyenpyrone and salicylic acid, so to prevent transdermal absorption poisoning.
(2) Oral administration Gastrointestinal absorption can vary greatly depending on individual differences or the nature of the drug, such as chloramphenicol, which is absorbed slowly and irregularly, and sulfonamides, which can be absorbed completely.
(3) Subcutaneous or intramuscular injection can affect the absorption distribution due to insufficient peripheral blood circulation, and is generally not used in newborns.
(4) Intravenous administration of intravenous drugs is the fastest absorption and reliable efficacy, but must take into account the volume of liquid, the physicochemical properties of the drug formulation and intravenous infusion fluid and the speed of infusion. Most intravenous drugs can be safely administered by nurses, but pentobarbital sodium, diazepam and other drugs with strong effects have the potential to cause acute poisoning when used, and should be accompanied by a physician. In addition, a few drugs such as propranolol and verapamil are more likely to cause danger than general drugs, so they should be administered more carefully.
2.The influence of body fluid distribution
The total volume of body fluids in newborns accounts for 80% of body mass (60% in adults), which is relatively higher than that in adults, so the concentration of water-soluble drugs decreases after dilution in extracellular fluid, and the discharge is also slower. The distribution volume of kanamycin in preterm infants is smaller than that of mature infants, and thus the peak blood concentration is higher than that of mature infants. It can be seen that preterm infants, like neonates, are more likely to cause kanamycin toxicity than mature infants, which affects the auditory nerve and renal function.
3. The effect of plasma protein binding rate
The low plasma protein binding in neonates is not only due to hypoproteinemia in neonates, but mainly because the drug does not bind easily to plasma proteins because of the change in the nature of plasma proteins in neonates. In addition, the presence of bilirubin and free fatty acids in the blood weakens the plasma protein binding of acidic drugs.
Drugs that do not easily bind to plasma proteins in neonates include ampicillin, digoxin, indomethacin, phenobarbital, phenytoin sodium, salicylates, etc. Sulfonamides can compete with bilirubin for binding to plasma proteins, and because the affinity of sulfonamides for albumin is stronger than bilirubin, the free bilirubin component in the blood of jaundiced children increases after application, and the ability to metabolize and excrete bilirubin is low, coupled with the poor blood-brain barrier in neonates This, coupled with the poor function of the blood-brain barrier in newborns, leads to the invasion of free bilirubin into the brain tissue and even causes nuclear jaundice. Sodium curry, chlorpromazine, vitamin K, vitamin K nalidixic acid, furantin, neomycin, primaquine, sulfonamides can promote the occurrence of neonatal jaundice or nuclear jaundice.
4, the influence of enzymes
Neonatal enzyme system is still immature, some drug metabolizing enzymes secretion is low and activity is insufficient, such as hydrolysis, oxidation and reduction and other biochemical reactions are low. For example, after neonatal application of chloramphenicol, due to the lack of glucuronosyltransferase combined into inactive derivatives, resulting in increased free chloramphenicol in the blood, making the newborn’s skin gray, causing gray baby syndrome; neomycin also has the effect of inhibiting glucuronosyltransferase, which can cause hyperbilirubinemia; sulfonamides and furans can also cause hemolysis in neonates with glucuronosyltransferase deficiency.
Therefore, the maturation of liver enzymes should be taken into account when medicating newborns, and the liver’s ability to process drugs generally approaches adult levels only after 2 weeks of life. If the jaundice of newborns does not subside, it means that their liver drug enzymes have not yet played an adequate role in detoxification, and they should promptly ask the doctor to deal with them or give enzyme inducers (such as phenobarbital for nuclear jaundice) to produce enzymatic effects to make bilirubin excretion.
5, renal function impact
The effective circulating blood volume and glomerular filtration rate of neonatal kidneys are 30% to 40% lower than those of adults, and the outline rate of penicillin C is only 17% of that of 2-year-old children. The excretion of many drugs is affected by the low glomerular filtration in neonates, resulting in high serum drug concentrations and prolonged half-life. This situation is more pronounced in preterm infants and can even be altered by day of age. Penicillin C has a half-life of 3 h for those born 0-6 d, 1.7 h for those born 7-13 d, and 1.4 h for children older than 14 d, and only approaches that of adults at 1 to 2 months. The half-life of chloramphenicol in neonates is 250 h, while in adults it is only 4 h. Therefore, the dose of the drug cannot be the same in neonates or children. In general, neonates should be given smaller amounts of drugs and the interval should be extended appropriately. These drugs are aminoglycosides, digoxin, furosemide, indomethacin, penicillin and furans. It takes 8 to 12 months for the maturation process of renal function in neonates to reach adult levels.
Second, the characteristics of drug use in infancy and early childhood
Oral administration of drugs to syrup is appropriate; oil drugs should be noted, must not be given to sleeping, crying or struggling infants to feed drugs, so as not to cause oil aspiration pneumonia; suspensions should be fully shaken before use. Because of the poor swallowing ability of infants, and most of them refuse to cooperate with parents to take drugs voluntarily, when necessary or to the dying child using injection methods, but intramuscular injection can affect the absorption of drugs due to insufficient local blood circulation, so commonly used intravenous injection and intravenous drip. When taking enteric tablets or controlled-release tablets, they cannot be crushed, otherwise their efficacy decreases, causing irritation and nausea and vomiting.
The nervous system is immature in infancy and early childhood. The disease often has irritability, high fever and convulsions, and sedatives can be added appropriately. For the dosage of sedatives, the younger the age, the greater the tolerance, the dose can be relatively large. However, infants and children to morphine, pethidine and other narcotic drugs easily cause respiratory depression, should not be applied. Although aminophylline is not a stimulant, but all have the effect of excitation of the nervous system, should also be used with caution.
Third, the characteristics of drug use in childhood
Children are in the stage of growth and development, their metabolism is vigorous, and the excretion of general drugs is relatively fast. However, attention should be paid to the prevention of water-electrolyte balance disorders, because children’s metabolism of water and electrolytes is still poor, such as long-term or large amounts of acid-base drugs, more likely to cause imbalance, the application of diuretics can also be low sodium, low potassium phenomenon, so the drug should be given intermittently, and the dose should not be too large.
Hormonal drugs should be used with caution: in general, try to avoid the use of adrenocorticosteroids such as cortisone and prednisone; the long-term application of androgens can cause premature closure of the skeleton, affecting the growth and development of children. Bone and tooth development are easily affected by drugs, such as tetracycline, which can cause enamel dysplasia and yellowing of tooth coloring. Tetracycline antibiotics are prohibited for pregnant and lactating women and children under 8 years old.
Fourth, the current pediatric drug use in some common problems
The physiological characteristics of children, especially newborns, determine the process of drugs in the body is different from that of adults. Because of the specialization and complexity of medication, thus requiring more careful consideration in drug varieties, doses, specifications, usage, etc. Currently, the dosage form specifications of some domestic drugs are incomplete or even unsuitable for clinical use in pediatrics, thus causing certain difficulties in the treatment of children. Many people mistakenly regard pediatric medication as a reduction of adult medication, resulting in the adultization of pediatric medication, resulting in many problems.
1.Irrational use of antibacterial drugs
At present, the abuse of antibacterial drugs is more prominent, non-infectious diseases such as intestinal cramps, simple diarrhea and general cold and fever, without investigating the cause, the first use of antibiotics, some even use expensive third-generation cephalosporins. According to statistics, in the treatment of upper respiratory tract infections or common cold, the use of antibiotics up to 99%, for emergency children, some first give gentamicin, said “insurance, do not need skin testing”, but did not know that led to serious consequences of nephrotoxicity and ototoxicity.
In addition, for infectious diarrhea in pediatrics, some inappropriately give antibiotic treatment, in fact, infectious diarrhea in infants and children is rotavirus and enterotoxic Escherichia coli infection, the use of antibiotics can neither shorten the course of the disease, nor reduce the symptoms of diarrhea, but rather lead to the generation of drug-resistant strains and secondary infection. The quinolones have become one of the leading antibiotics since the 20th century because of their broad antibacterial spectrum and strong antibacterial action, but they can cause damage to the bone and joint, especially the cartilage tissue of weight-bearing joints, in young dogs and other mammals. However, the clinical reality is that it is more commonly used in children under 12 years of age and pregnant women, and the dosage is large.
2, antipyretic and analgesic drug abuse
At present, compound preparations containing pyrazolones (such as aminophenazone tablets, analgesic tablets, painkillers, and painkillers, etc.) are still available for sale, and their antipyretic and analgesic effects are sure, but they should not be taken for a long time, especially for children, who are prone to aplastic anemia and purpura, and should have their blood checked before and after the drug is used. In the stomach to form mucosal decay.
According to data from the United Kingdom, the United States, and other countries, the use of aspirin in febrile children is closely related to the development of Rege’s syndrome, a common acute brain disease associated with fatty changes in the liver that can occur after viral infections such as colds and chickenpox, with a mortality rate of up to 50%. For example, the use of cold and flu can cause hematuria in children because one of its components, diclofenac, can inhibit the synthesis and release of prostaglandins, so it should be prohibited for children with renal insufficiency at the stage of growth and development. Acetaminophen is currently the most widely used antipyretic and analgesic drug, its efficacy, adverse reactions, oral absorption is rapid and complete, but the dose should not be increased, children under 3 years of age should be used with caution.
3, the trace elements and vitamins as absolutely safe nutrition medicine
Many parents of only children and some physicians regard trace elements and vitamins as “nutritional drugs” and take them for a long time or in large doses, for example, trace elements of zinc, the concentration of which reaches 15 mg/L has the ability to damage macrophages and kill fungi, which can increase the incidence of sepsis. Therefore, when supplementing with zinc, attention should be paid to the complications that may accompany it. Vitamins should be taken according to the body’s needs, but abuse and excessive long-term use can lead to toxic side effects. For example, some parents use cod liver oil as a “tonic” for children for a long time, or use too much vitamin D in the prevention and treatment of rickets, resulting in high concentrations of vitamin AD in the body and chronic toxic symptoms such as peripheral discomfort, gastrointestinal reactions, headache, bone and joint pain, and hypercalcemia.
4.Long-term infusion of large amounts of glucose injection glucose injection has nutritional, detoxification, cardiac and diuretic effects
Many hospitals use 10% glucose injection as the common basic solution for newborns, but too fast an input can cause neonatal hyperglycemia. The maximum reabsorption of glucose by the renal tubules of newborns is only 1/5 of that of adults, and the tolerance to sugar is low, the function of pancreatic islet cells is incomplete, and the activity of insulin is low, thus too fast or persistent intravenous drip can cause medical hyperglycemia and even intracranial hemorrhage due to intracranial vasodilation.
V. Precautions for pediatric drug use
As pediatric patients are in a period of continuous development in all aspects such as physical fitness and organ function, the safety of medication is receiving more and more attention and attention. Therefore, pediatric medication should pay attention to the following issues.
1. Familiarity with pediatric characteristics, no drug abuse
Understand the anatomical and physiological characteristics of children in different developmental periods, special reactions to drugs, master the indications for drug use, and rational use of drugs. Particular attention should be paid to the abuse of antibiotics, vitamins, antipyretics and analgesics and gammaglobulin in rural areas and primary care units.
2. Strictly grasp the dose and pay attention to the interval time
The dosage of drugs should vary with the maturity and condition of children. In recent years, the proportion of obese children has increased, and the blood concentration measurement found that the blood concentration is often too high when the dose is calculated according to the traditional body mass, so the individualized dosing of obese children is a new topic of research.
In addition, we should pay attention to the administration interval, do not give too many times, too often, especially in the efficacy or suspected overdose, should monitor the blood concentration to adjust the dose and interval time.
3, according to the characteristics of children, choose a good route of drug delivery
Generally speaking, it is safer to administer drugs through the stomach, and oral administration should be used as much as possible. The volume of subcutaneous injection for newborns is very small, and the drug can damage the surrounding tissues and be poorly absorbed, so it is not suitable for newborns. Larger infants and children have better circulation and can be injected intramuscularly. Infants and young children must be given intravenously according to the prescribed speed drip, not too fast and too urgent, and to prevent drug exudation caused by tissue necrosis, do not repeatedly apply the same vessel to prevent thrombophlebitis. Infants and children with thin skin keratinization layer, the drug is very easy to transdermal absorption and even poisoning, so do not take too long to administer topical medication.
4, pediatric prohibited or caution chemical drugs
Aspirin, indomethacin, chloramphenicol, tetracycline, kanamycin, neomycin, streptomycin, chlorpromazine, fenadine, phenobarbital, chlorhexidine hydrate, diazepam, clorazepam (Librium), reserpine, dimercaptopropanol, vitamin K methylene blue, methyltestosterone, sodium benzoate caffeine, pediculine, trichothecene, digoxin, methanesulfonylurea, furosemide, etc.
In conclusion, the pediatric population is in an important stage of growth and development, and has obvious characteristics in anatomy, physiology and pathology. Many organs (such as heart, liver and kidney) and nervous system functions are still incompletely developed and extremely sensitive to many drugs. And the pediatric intestinal tube is relatively long, the digestive tract area is relatively large, the intestinal wall is thin, the mucosa is rich in blood vessels, permeability, high absorption rate, low glomerular filtration rate, poor excretion function. Moreover, children have certain requirements for the color, aroma, taste and appearance of drugs from the psychological point of view, so the administration of drugs to children should be closely linked with pharmacology, physiology and psychology.