Chapter 10 - Drug Therapy In Pediatrics

CHAPTER 10

DRUG THERAPY

IN

PEDIATRIC PATIENTS

Patients who are very young or very old respond differently to drugs than anyone. quantitative differences – patients in both age groups are more sensitive to drugs than other patients, and they show greater individual variation organ system immaturity – drug sensitivity results largely in the very young organ system degeneration – drug sensitivity results largely in the elderly Pediatrics covers all patients under the age of 16. - because of ongoing growth and development, pediatric patients in different age groups present different therapeutic challenges Pediatric 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 - pediatric drug therapy is made even more difficult by insufficient drug information - until recently, FDA did not require drug trials in children - despite lack of good information, the clinician must nonetheless use drugs to treat pediatric patients

I.

PHARMOCOKINETICS: NEONATES

AND

INFANTS

- pharmacokinetic factors determine the concentration of a drug at its sites of action; hence determining the intensity and duration of response - elevated drug levels, responses will be more intense - delayed drug elimination, responses will be prolonged - because the organ systems that regulate drug levels are not fully developed in the very young, they are at risk for both intense and prolonged responses Administration Route Differences: IV administration – drug levels decline more slowly in infants - drug levels remain above the MEC longer causing effects to be prolonged Subcutaneous Administration – not only do drug levels in infants remain above the MEC longer

but these levels also rise higher, causing effects to be more intense as well as more prolonged - adjustment of dosage for infants on the basis of body size alone is not sufficient to achieve safe results

A.

SENSITIVITY

DUE TO

IMMATURE STATE

OF

PROCESSES

1.

Absorption a. oral administration - gastric emptying time is both prolonged and irregular in early infancy - reaches adult values by 6 to 8 months - from the stomach, delayed gastric absorption is delayed - gastric acidity is very low 24 hours after birth - does not reach adult values for 2 years - absorption of acid-labile drugs is increased b. intramuscular administration - IM injection in the neonate is slow and erratic - delayed absorption is due in part to low blood flow through muscle during the first days of postnatal life - by early infancy, absorption of IM drugs becomes more rapid than in neonates and adults c. percutaneous absorption - because the skin of the very young is thin, percutaneous drug absorption is significantly greater than in older children and adults - increases the risk of toxicity from topical drugs 2.

Distribution a. protein binding - plasma proteins are limited in the infant because the amount of albumin is relatively low and endogenous compounds (e.g., fatty acids, bilirubin) compete with drugs for available binding sites - concentration of free levels of such drugs is relatively high in the infants, intensifying effects - reaches adult values within 10 to 12 months b. blood-brain barrier

- not fully developed at birth - drugs and other chemicals have relatively easy access to the CNS, making the infant especially sensitive to drugs - ex. glucocorticoids can effect growth through the hypothalamus tetratcyclines effect teeth by staining them aspirin should not be given with chicken pox or flu-like symptoms B.

HEPATIC METABOLISM - drug metabolizing capacity of newborns is low - neonates are especially sensitive to drugs that are eliminated primarily by hepatic metabolism - capacity of the liver to metabolize many drugs increases rapidly about 1 month after birth with compete maturation of the liver by 1 year C.

RENAL EXCRETION - significantly reduced at birth - renal blood flow, glomerular filtration, and active tubular secretion are all low during infancy - drugs that are eliminated primarily by renal excretion must be given in reduced dosage - adult levels are reached by 1 yrear

II.

PHARMACOKINETICS: CHILDREN 1

YR AND

OLDER

- by the age of 1 year, most pharmacokinetic parameters in children are similar to those of adults - drug sensitivity in children over the age of 1 is more like that of adults - one important difference is that they metabolize drugs faster than adults (which is markedly elevated until the age of 2)

III.

DOSAGE DETERMINATION

Method of conversion employed most commonly is based on body surface area: Approximate child’s dose = Body surface area of the child X Adult dose 1.73 m2 - initial doses are at best an approximation - there is no standard - compliance is essential in administering medication to pediatrics

IV.

PROMOTING COMPLIANCE Issues to Address: • dosage size and timing • route and technique of administrations • duration of treatment • drug storage • nature and time course of desired and adverse responses

- techniques of administration that are difficult, a demonstration should be made, after which the parents should repeat the procedure to ensure they understand - with young children, spills and spitting out are common causes of inaccurate dosage - parents should be instructed to complete the full treatment Additional Compliance Promotional Tools: • selecting the most convenient dosage form and dosing schedule • suggesting mixing oral drugs with food or juice (when allowed) to improve palatability • providing a calibrated medicine spoon or syringe for measuring liquid formulations • taking extra time with young or disadvantaged parents to help ensure conscientious and skilled participation