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SAFETY AND BASIC RULES FOR USING MEDICINES IN YOUNG CHILDREN
¹Usmonova Zarina Muxtor qizi
²Xoldorov Habibulloh Olimjon oʻgʻli
³Uralov Anvar Abdurashidovich
¹Assistant Professor, Department of Clinical Pharmacology, Samarkand State Medical
University
²'³Students of Samarkand State Medical University
https://doi.org/10.5281/zenodo.14787239
Abstract.
Decreased gastric acid secretion increases the bioavailability of acid-sensitive
drugs (e.g., penicillins) and decreases the bioavailability of weakly acidic drugs (e.g.,
phenobarbital).
Decreased bile acids reduce the bioavailability of lipophilic drugs (e.g. diazepam).
When enteral medications are administered to infants younger than 3 months of age,
delayed gastric emptying and intestinal motility increase the time required to reach therapeutic
concentrations. Drug-metabolizing enzymes present in the infant's intestines are another reason
for reduced drug absorption. Infants with congenital intestinal atresia, those who have had their
intestines surgically removed, and those who require the use of a jejunal feeding tube may have
specific malabsorption depending on the size and location of the missing or bypassed intestine.
You should also consider how the type of food you are eating may affect gastric emptying (e.g.,
solid or liquid).
Keywords:
Drugs, Effects, Side effects, Drug use in young children.
INTRODUCTION
Changes in the intestinal flora that stimulate metabolism can also affect the absorption
process in the intestine.
a.
The absorption of injectable forms of drugs often varies for the following reasons:
b.
The variability of their chemical properties
c.
differences in absorption at the injection site depending on the route of
administration (intramuscular or subcutaneous);
d.
Muscle mass variability in children
e.
the presence of a disease (for example, circulatory disorders);
f.
Variation in injection depth (too deep or too shallow)
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Intramuscular injections in children are generally avoided due to the associated pain and
potential for tissue damage, but if necessary, water-soluble preparations are recommended because
they do not form a precipitate at the injection site.
Transdermal absorption through the skin may be increased in newborns and young children
because the cornea is thinner and the surface area to div mass ratio is significantly higher than
in older children and adults. Skin lesions (e.g. furunculosis, eczema, burns) increase transdermal
absorption in children of any age.
Rectal administration is usually used in special cases where intravenous administration is
not possible (e.g. rectal administration of diazepam in epileptic status). Due to differences in
venous drainage systems, administration into the rectal cavity may result in changes in absorption.
In infants, the drug may be excreted from the div before significant absorption occurs.
The absorption of inhaled medications in the lungs (e.g., beta-agonists in the treatment of
asthma, pulmonary surfactant in respiratory distress syndrome) may depend less on physiological
parameters and more on the reliability of the delivery device and the technique of using such a
device by the patient or caregiver.
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The volume of distribution of drugs varies with age in children. These age-related
characteristics are due to changes in the composition of div tissues (especially extracellular
substances and total fluid volume) and binding to plasma proteins.
Younger children require higher doses (per kg of div weight) of water-soluble drugs
because water makes up a higher percentage of their div weight (see “Body Changes During
Growth and Aging”). Conversely, as children age, because extracellular fluid volume decreases,
lower doses of water-soluble drugs are required to avoid toxicity. In addition, obese children have
been shown to have significantly higher total div water, div volume, lean div mass, and
percentage of fat mass compared with nonobese children ( 1 ).
Changes in the div during growth and aging
Many drugs are bound to proteins (mainly albumin, α1-acid glycoprotein, and
lipoproteins); protein binding limits the distribution of free drug throughout the div. Albumin
and total protein concentrations are low in newborns but reach adult levels by 10–12 months of
age. The reduced protein binding in newborns is also due to qualitative differences in plasma
proteins and competitive binding with other molecules, such as bilirubin and free fatty acids, which
circulate in higher concentrations in the plasma of newborns and infants. The net result may be
increased free drug concentrations, greater availability of drug substrates for receptors, and
increased adverse effects at lower drug concentrations.
The metabolism and excretion of drugs vary with age and depend on the substrate or drug,
but for most drugs, especially phenytoin, barbiturates, analgesics, and cardiac glycosides, the
plasma half-life in neonates is 2 to 3 times longer than in adults.
1.
The cytochrome P-450 (CYP450) enzyme system in the small intestine and liver is
the most important known drug metabolism system. CYP450 enzymes inactivate drugs in the
following ways:
2.
Oxidation, reduction and hydrolysis (phase I of metabolism)
3.
Hydroxylation and conjugation (phase II of metabolism)
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RESEARCH METHODS AND APPROACHES
In newborns, the metabolic activity of phase I decreases, gradually increases until 6 months
of age, exceeds adult levels for some drugs in the first few years of life, slows down during
adolescence, and usually reaches adult levels by adulthood. However, for some drugs (e.g.,
barbiturates, phenytoin), adult metabolic rates can be reached 2–4 weeks after birth. CYP450
activity can also be induced (decreased drug concentration and effect) or inhibited (increased
concentration and effect) by concomitant drug administration. Drug interactions can lead to both
toxicity when CYP450 activity is reduced and inadequate drug effect when CYP450 activity is
increased. Diet also influences the increase in CYP450 activity in children ( 1 ). The kidneys,
lungs, and skin also play a role in the metabolism of some drugs, as do intestinal enzymes that
facilitate drug metabolism in newborns.
Phase II metabolism varies considerably depending on the substrate. The maturation of the
enzymes responsible for the conjugation of bilirubin and acetaminophen is delayed; the enzymes
responsible for the conjugation of morphine are fully active even in premature infants.
Drug metabolites are excreted primarily through the bile or kidneys. Renal excretion
depends on:
Глава 1
From binding to plasma proteins
Глава 2
Renal blood flow
Глава 3
From the glomerular filtration rate
Глава 4
Tubular secretion
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RESEARCH RESULTS
All of these factors change during the first 2 years of life. Renal plasma flow is low at birth
(12 ml/min) and reaches adult levels of 140 ml/min by 1 year of age. Similarly, glomerular
filtration rate is 2–4 ml/min at birth, increasing to 8–20 ml/min within 2–3 days and reaching adult
levels of 120 ml/min by 3–5 months of age.
Drug dosage
Because of the above factors, the dosage of a drug in children under 12 years of age is often
based on age, div weight, or both. This approach is practical but not ideal. Even in a population
of children of the same age and weight, the need for a drug may vary depending on the maturation
of the absorption, metabolism, and elimination processes. Thus, in practice, dosage adjustments
should be based on plasma drug concentrations (however, plasma drug concentrations may not
correspond to target organ drug concentrations). Unfortunately, for many drugs, these adjustments
are not possible. However, in the United States, the passage of the Children's Best Drugs Act of
2001 and the Children's Fair Research Act of 2003 (both laws became permanent in 2012 [ 1 ])
has resulted in the availability of pediatric data on dosage, pharmacokinetics, and safety for more
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than 900 drugs for use in children (see also the U.S. Food and Drug Administration [FDA] 2020
Status Report).
Physiologically based pharmacokinetic modeling is a mathematical technique that uses
known principles of biochemistry and physiology to predict how a drug will be absorbed,
distributed, metabolized, and excreted. The results of such modeling can help inform decisions
about when and how to conduct a clinical trial and help improve the safety and effectiveness of
pediatric clinical trials.
The following English language resource may be informative. Please note that the guide is
not responsible for the content of this resource.
Non-adherence to medication recommendations (see also: "Adherence to prescribed
medication therapy") can occur at any age for a variety of reasons, including:
a.
Painful or uncomfortable management method
b.
The need for frequent doses, complex dosing regimens, or both.
c.
However, many unique factors contribute to treatment nonadherence in children.
d.
Children under 6 years of age may have difficulty swallowing pills and may resist
taking medications that have an unpleasant taste.
Older children often resist taking medications and using treatment regimens (e.g., insulin,
metered-dose inhalers), which requires them to leave class or stop activities, making them stand
out from their peers.
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Adolescents may protest and assert independence from parents/guardians by refusing to
take medication. They may also skip doses of medication without experiencing any side effects
and then falsely reason that they do not need the prescribed medication, thus becoming
increasingly disengaged. Adolescents want to be like their friends and fit in with their peers. They
may wear the same clothes, prefer the same sneakers, and eat the same foods as their peers. Having
a chronic illness sets them apart from their peers, and they often refuse to seek treatment so as not
to appear “different” to their friends.
Parents/caregivers may not always remember medication instructions, may not understand
the rationale for the prescription, and may have work schedules that do not allow them to give
their children the prescribed doses. Some people try home remedies or herbal remedies first. Some
have limited incomes and are forced to spend their money on other priorities, such as food; others
have beliefs and attitudes that prevent them from giving their children medication.
Adolescents in particular should be encouraged to feel in control of their illness and
treatment and to communicate freely, allowing them to take responsibility for their own treatment
as much as possible.
CONCLUSION
Simplifying regimens (e.g., synchronizing multiple medications and reducing the
frequency of daily dosing while maintaining efficacy) and adapting them to the patient and
caregiver's regimen are recommended. Important aspects of treatment (e.g., completing the full
course of antibacterial medication) should be emphasized. If lifestyle changes (e.g., diet or
exercise) are necessary, these changes should be introduced gradually over several visits to the
specialist, and the proposed goals should be realistic so as not to overwhelm the patient or
caregiver. Success should always be rewarded and reinforced with praise, and only then can the
next goal be set.
Drug therapy for children differs from that for adults, primarily because pediatric dosing is
usually based on weight or div surface area ( 1 ). Doses (and dosing intervals) vary with age
because of age-related changes in drug absorption, distribution, metabolism, and excretion (see
Pharmacokinetics in Children) ( 2 ). Therefore, adult doses are not given to children. Furthermore,
pediatric dosing cannot be considered to be proportional to adult dosing (i.e., you cannot give a 70
kg child 1/10th the adult dose).
Most drugs have not been adequately studied in children, but in the United States, laws
such as the Best Drugs for Children Act of 2001 and the Pediatric Research Act of 2003 (both of
which were made permanent in 2012[ 3 ]) now provide legislative and regulatory authority to
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encourage and conduct therapeutic research in children. These actions have resulted in numerous
changes to labeling to provide dosing, pharmacokinetics, and safety information for children (see
also the U.S. Food and Drug Administration [FDA] 2020 report).
Children generally develop the same side effects as adults (see "Adverse Drug Reactions"),
but the risk of developing side effects with some drugs is significantly higher in pediatrics because
of differences in pharmacokinetics and the potential effects of drugs on growth and development.
Some common drugs with a rare or high risk of side effects in children are listed in the table of
some drugs that cause various toxic reactions in children.
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