Drug Therapy in Pediatric Patients (Ch. 10) NOTES

Additional ways to promote adherence include

(1) selecting the most convenient dosage form and dosing schedule, (2) suggesting mixing oral drugs with food or juice (when allowed) to improve palatability, (3) providing a calibrated medicine spoon or syringe for measuring liquid formulations, and (4) taking extra time with parents to help ensure conscientious and skilled participation.

*Binding of drugs to albumin* and other plasma proteins is LIMITED IN THE INFANT, b/c

(1) the amount of serum albumin is relatively low and (2) endogenous compounds (eg, fatty acids, bilirubin) compete with drugs for available binding sites.

For drugs that are *absorbed* primarily from the *stomach*,

*delayed gastric emptying enhances absorption*.

The capacity of the liver to metabolize many drugs increases rapidly about ____________, and approaches adult levels a few months later.

1 month after birth Complete maturation of the liver develops by 1 year.

*Renal drug excretion* is significantly *reduced at birth*.

1. Renal blood flow 2. glomerular filtration, 3. active tubular secretion are all *low during infancy*.

To help expand our knowledge of drugs in peds, Congress enacted two important laws:

1. the Best Pharmaceuticals for Children Act (BPCA), passed in 2002 2. Pediatric Research Equity Act (PREA) of 2003. Both were designed to promote drug research in children.

Protein-binding capacity reaches adult values within

10 to 12 month from birth

Drug-metabolizing capacity is markedly elevated FROM 1 YEAR until age

2 years, and then gradually declines.

Gastric acidity is very low 24 hours after birth and does not reach adult values for

2 years.

When does gastric emptying gradually reach adult values in the very young?

6 to 8 month

When administering a medication known to be metabolized by the liver, the nurse will closely monitor for adverse drug reactions in which patient? A 3-month-old infant A 12-month-old infant An 18-month-old toddler A 13-year-old adolescent

A 3-month-old infant

Which statement about intramuscular (IM) administration is incorrect? Drug absorption following IM injection in the neonate is slow and erratic. Absorption of IM drugs becomes more rapid in infancy than in neonates. Neonates experience low blood flow through muscle during the first days of postnatal life. Absorption of IM drugs becomes slower and more erratic in infancy than in neonates.

Absorption of IM drugs becomes slower and more erratic in infancy than in neonates.

Which statement about renal excretion in infants is true? Renal blood flow is high during infancy. Renal drug excretion is significantly increased at birth. Adult levels of renal function are achieved by 1 year. Drugs that are eliminated primarily by renal excretion must be given in higher doses.

Adult levels of renal function are achieved by 1 year.

For medications that do not have established pediatric doses, the most common method of extrapolating the appropriate dose is based on which measurement?

BSA

The stratum corneum of the INFANTS skin is very thin, and blood flow to the skin is greater in infants than in older patients.

Because of this enhanced absorption, infants are at increased risk of toxicity from topical drugs.

Kernicterus

Bilirubin encephalopathy, a form of brain damage resulting from unconjugated bilirubin entering the brain. Characterized by lethargy, poor feeding, vomiting, irregular respiration, perhaps death

ADVERSE EFFECT: Sudden infant death syndrome

DRUG: *Pheno*THIAZINES

ADVERSE EFFECT: Severe intoxication from acute overdose (acidosis, hyperthermia, respiratory depression); Reye's syndrome in children with chickenpox or influenza

DRUG: Aspirin and other salicylates

ADVERSE EFFECT: Gray syndrome (neonates and infants)

DRUG: Chloramphenicol

ADVERSE EFFECT: Tendon rupture

DRUG: Fluoroquinolones

ADVERSE EFFECT: Growth suppression with prolonged use

DRUG: Glucocorticoids

ADVERSE EFFECT: Central nervous system toxicity (infants)

DRUG: Hexachlorophene

ADVERSE EFFECT: Cartilage erosion

DRUG: Nalidixic acid

ADVERSE EFFECT: Pronounced respiratory depression in children under 2 years old

DRUG: ProMETHazine

ADVERSE EFFECT: Kernicterus (neonates)

DRUG: Sulfonamides

ADVERSE EFFECT: Staining of developing teeth

DRUG: Tetracyclines

The nurse is caring for a group of very young patients receiving a variety of medications. Which concept guides the nurse's care of these patients? Drugs given intravenously (IV) leave the body more quickly in infants than in adults. Drugs given subcutaneously (SC) remain in the body longer in infants than in adults. Gastric emptying time is shorter in infants than in children and adults. The blood-brain barrier protects the infant's brain from toxic drugs.

Drugs given subcutaneously (SC) remain in the body longer in infants than in adults.

By _______ ________, absorption of IM drugs becomes more rapid than in neonates and adults.

EARLY INFANCY

In children 1 year and older, most pharmacokinetic parameters are similar to those in adults.

Hence, drug sensitivity is more like that of adults than the very young.

Low gastric acidity in the very young (24hours- 2years)

INCREASES the absorption of *acid-labile drugs* (**Remeber that acidic drugs are best asbored in a more alkaine enviroment)

Pharmacokinetics: Neonates and Infants *Pharmacokinetic factors* determine the *concentration of a drug at its sites of action*, and hence determine the intensity and duration of responses.

If drug levels are elevated, responses will be more intense. If drug elimination is delayed, responses will be prolonged (true in all ages)

GASTRIC EMPTYING time is both

PROLONGED & IRREGULAR in EARLY INFANCY, and then *gradually reaches adult values by 6 to 8 months*.

With some disorders—especially infections—symptoms may resolve before the prescribed course of treatment has been completed.

Parents should be instructed to complete the full course nonetheless.

DRUG = Androgens ADVERSE EFFECT =

Premature puberty in males; reduced adult height from premature epiphyseal closure

Which intervention would the nurse choose to minimize the risk of drug toxicity in neonates and infants? Reduce the amount of drug given. Administer the medication before meals. Shorten the interval between doses. Administer the medication intravenously.

Reduce the amount of drug given.

Drug absorption following IM injection in the neonate is .

SLOW & ERRATIC

Why are infants especially sensitive to drugs that affect CNS function? The blood-brain barrier is especially strong in infants. The blood-brain barrier does not exist until 1 year of age. The blood-brain barrier is not fully developed at birth. The blood-brain barrier is weakened by the birth process.

The blood-brain barrier is not fully developed at birth.

why should all medicines employed for their CNS effects (eg, morphine, phenobarbital) should be given in reduced dosage for INFANTs?

The blood-brain barrier is not fully developed at birth. As a result drugs and other chemicals have relatively easy access to the CNS, making the infant especially sensitive to drugs that affect CNS function.

If small body size is not the major reason for heightened drug sensitivity in infants, what is?

The increased sensitivity of infants is due largely to the *immature state of five pharmacokinetic processes*: (1) drug absorption, (2) protein binding of drugs, (3) exclusion of drugs from the central nervous system (CNS) by the blood-brain barrier, (4) hepatic drug metabolism, and (5) renal drug excretion.

Please note that initial pediatric doses—whether based on established pediatric doses or extrapolated from adult doses—are at best an approximation. Subsequent doses must be adjusted on the basis of 1. clinical outcome 2. plasma drug concentrations.

These adjustments are especially important in *neonates and younger infants*. If dosage adjustments are to be optimal, it is essential that we monitor the patient for therapeutic and adverse responses.

Although pharmacokinetically similar to adults, children do differ in one important way:

They metabolize drugs faster than adults.

The nurse is teaching young parents about medication administration in their child. Which statements are appropriate to include in the teaching plan? Select all that apply. "Guard against spills and spitting to ensure that your child gets an accurate dose." "Do not mix your child's medication with food or drink." "This calibrated spoon will help your child get an accurate dose." "Keep a medication record to make sure you do not give more than one dose at a time." "If your child spits some medication out, give another full dose at that time."

This calibrated spoon will help your child get an accurate dose." " "Guard against spills and spitting to ensure that your child gets an accurate dose." Keep a medication record to make sure you do not give more than one dose at a time."

Which of the following is not an example of age-related adverse drug effects? Growth suppression Discoloration of developing teeth Kernicterus Toxicity

Toxicity

Because of heightened drug sensitivity, they are at increased risk of

adverse drug reactions.

When more than one person is helping medicate a child,

all participants should be warned against multiple dosing.

Why should *Dosage be reduced in infants for drugs used for actions outside the CNS if those drugs are capable of producing CNS toxicity as a side effect*.

b/c the BBB is not fully developed at birth Therefore, drugs that have the ability to produce CNS toxicity can more easily gain assess to areas that could cause harm

When a drug is administered *subcutaneously,* not only do levels in the infant remain above the MEC longer than in the adult,

but these levels also rise higher, causing effects to be more intense as well as prolonged.

acid labile drugs

destroyed by stomach acid (WHEN pH is normal - Like in adults. B/C acid labile drugs prefer a more alkaline environment to promote asorbtion)

Because of the pharmacokinetic factors discussed previously, dosage selection for pediatric patients is difficult. Selecting a dosage is especially difficult in the very young, since pharmacokinetic factors are undergoing rapid change. Pediatric doses have been established for a few drugs but not for most. For drugs that do not have an established pediatric dose,

dosage can be extrapolated from adult doses. The method of conversion employed most commonly is based on body surface area (BSA): (child's BSA * adult dosage) / 1.73 meters squared = pedatric dose

equivalent doses

doses adjusted for body weight

*Gastrointestinal physiology* in the infant is very different from that in the adult. As a result,

drug absorption may be enhanced or impeded, depending on the physicochemical properties of the drug involved.

When a drug is administered *intravenously*, levels decline more slowly in the infant than in the adult. As a result,

drug levels in the infant remain above the minimum effective concentration (MEC) longer than in the adult, thereby causing effects to be prolonged.

▪ In neonates and young infants,

drug responses may be unusually intense and prolonged.

The blood-brain barrier is not fully developed at birth. As a result,

drugs and other chemicals have relatively easy access to the CNS, making the infant especially sensitive to drugs that affect CNS function.

▪ Renal excretion of drugs is low in neonates. Thus,

drugs that are eliminated primarily by the kidney must be given in reduced dosage and/or at longer dosing intervals.

▪ Protein-binding capacity is limited early in life, so

free concentrations of some drugs may be especially high.

On the other hand, for drugs that are *absorbed* primarily from the *intestine*, absorption is delayed when

gastric emptying is delayed

Because the drug-excreting capacity of infants is limited, drugs that are eliminated primarily by renal excretion must be

given in reduced dosage and/or at longer dosing intervals. Adult levels of renal function are achieved by 1 year.

Because of organ system immaturity, very young patients are

highly sensitive to drugs.

Because of enhanced drug metabolism in children, an

increase in dosage or a reduction in dosing interval may be needed for drugs that are eliminated by hepatic metabolism.

It is clear that adjustment of dosage for infants on the basis of body size alone

is not sufficient to achieve safe results.

Delayed absorption of IM INJECTIONS of NEONATES is due in part to

low blood flow through muscle during the first days of postnatal life.

Multiple dosing can be avoided by

maintaining a drug administration chart.

▪ Children (1 to 12 years) differ pharmacokinetically from adults in that children

metabolize drugs faster.

By age 1 year, most pharmacokinetic parameters in children are similar to those in adults. Therefore, drug sensitivity in children older than 1 year is

more like that of adults than that of the very young.

absorption of IM drugs in infants is

more rapid than in adults.

Stratum corneum (horny layer)

most superficial layer; dead cells filled with keratin (barrier area)

The blood-brain barrier is not fully developed at birth. Therefore,

neonates are especially sensitive to drugs that affect the CNS.

▪ The drug-metabolizing capacity of neonates is low, so

neonates are especially sensitive to drugs that are eliminated primarily by hepatic metabolism.

The *drug-metabolizing capacity of NEWBORNS is low*. As a result,

neonates are especially sensitive to drugs that are eliminated primarily by hepatic metabolism. When these drugs are used, dosages must be reduced.

Because gastric emptying time is irregular in the very young below 6-8 months, the precise impact on absorption is

not predictable.

Drug absorption *through the skin* is MORE RAPID and COMPLETE in INFANTS than in

older children and adults.

Drug sensitivity in the very young results largely from

organ system immaturity.

With young children, spills and spitting out are common causes of inaccurate dosing;

parents should be taught to estimate the amount of drug lost and to readminister that amount, being careful not to overcompensate.

▪ Absorption of IM drugs in neonates is

slower than in adults.

▪ Initial pediatric doses are at best an approximation. To ensure optimal dosing,

subsequent doses must be adjusted on the basis of clinical outcome and plasma drug levels.

Consequently, b/c *Binding of drugs to albumin* and other plasma proteins is LIMITED IN THE INFANT, drugs that ordinarily undergo extensive protein binding in adults undergo much less binding in infants. As a result,

the *concentration of free levels of such drugs is relatively high in the infant*, thereby *intensifying effects*. To ensure that effects are not too intense, dosages in infants should be reduced. Protein-binding capacity reaches adult values within 10 to 12 month

gastric emptying

the process by which food leaves the stomach and enters the small intestine

The majority of drugs used in pediatrics have never been tested in children. As a result,

we often lack reliable information on which to base drug selection or dosage.

Pharmacokinetics

what the body does to the drug (ADME)

A further sharp decline in Drug-metabolizing capacity takes place at puberty,

when adult values are reached.

Early studies revealed (after congress enacted laws in 2002)

• About 20% of drugs were ineffective in children, even though they were effective in adults. • About 30% of drugs caused unanticipated side effects, some of them potentially lethal. • About 20% of the drugs studied required dosages different from those that had been extrapolated from dosages used in adults.

Promoting Adherence Achieving accurate and timely dosing requires *informed participation of the child's caregiver and, to the extent possible, active involvement of the child as well*. Effective education is critical. The following issues should be addressed:

• Dosage size and timing • Route and technique of administration • Duration of treatment • Drug storage • The nature and time course of desired responses • The nature and time course of adverse responses *Written instructions* should be provided. For techniques of administration that are difficult, a *demonstration should be made*, after which the parents should *repeat* the procedure to ensure they understand.

Pediatrics covers all patients up to age *16 years* Because of ongoing growth and development, pediatric patients in different age groups present different therapeutic challenges. Traditionally, the pediatric population is subdivided into *six groups*:

• Premature infants (less than 36 weeks' gestational age) • Full-term infants (36 to 40 weeks' gestational age) • Neonates (first 4 postnatal weeks) • Infants (weeks 5 to 52 postnatal) • Children (1 to 12 years) • Adolescents (12 to 16 years)