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Pharmacology Outline Ch.

10

Drug therapy in pediatric patients

Quantitative differences – Patients in very old and very young age groups are more
sensitive to drugs than other patients and they show great individual variation

Young – Drug sensitivity in the very young is largely due to organ system
immaturity

Elderly – largely results from organ system degeneration

** Pediatrics covers all patients under the age of 16

6 groups:

– Premature infants (less than 36 wks gestation)


– Full term infants (36 – 40 weeks gestational age)
– Neonates (first 4 post natal weeks)
– Infants (wks 5 to 52)
– Children (1 to 12 years)
– Adolescents (12 to 16yrs)

As young patients grow older, they become more like adults physiologically and
more like adults w/regard to drug therapy

Under 1 year they differ greatly from adults

B/c we have insufficient drug info on peds, we have more difficulty w/ dosing,
pharmacokinetics, effects (therapeutic and adverse)

Pharmacokinetics: neonates and infants

– If drug levels are elevated, responses will be more intense


– If drug elimination is delayed, responses will be prolonged
– b/c the organ systems involved w/ both are not fully developed, both poss.
– When drug is administered intravenously, levels decline more slowly in the
infant than the adult
– When a drug is administered subcutaneously, not only do levels in the infant
remain above MEC longer than in the adult, but these levels also rise HIGHER,
causing effects to be more intense and prolonged

Increased sensitivity in infants is due to 5 pharmacokinetic processes:

– Drug absorption
– Protein binding of drugs
– Exclusion of drugs from CNS by BBB
– Hepatic drug metabolism
– Renal drug excretion

Absorption

Oral – GI physiology in infant is very different from adults, so drug absorption


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

– Gastric emptying time is both prolonged and irregular in early infancy, then
gradually reaches adult values by 6 to 8 mo.
– Delayed gastric emptying enhances absorption (for drugs absorbed in
stomach)
– Delays absorption in intestine
– Gastric acidity is very low 24 hours after birth and does not reach adult
values for 2 years, so absorption of acid labile drugs is increased

IM admin – drug absorption following IM injection in neonate is slow and erratic.

– Delayed absorption is due in part to low blood flow through muscle during the
first days of post natal life.
– By early infancy, absorption of IM drugs becomes more rapid than in
neonates and adults

Percutaneous absorption – b/c skin of young is very thin, percutaneous drug


absorption is significantly greater than in older children and adults

– Increases risk of toxicity from topical drugs


– Percutaneous means – effected, occurring or pertaining to the skin

Distribution

Protein Binding
Binding of drugs to albumin and other plasma proteins is limited in the infant
because:
- the amt of albumin is relatively low
- endogenous compounds compete w/ drugs for available binding sites

– As a result, concentration of free levels of drugs is relatively high in the


infant, intensifying effects
– To ensure that effects are not too intense, dosage in infants should be
reduced
– Protein binding capacity reaches adult values w/in 10-12 mo.

Blood brain barriers


Not fully developed at birth.
- as a result, many drugs and other chemicals have relatively easy access to the
CNS
- All medicines used for CNS effects (opioids, etc) should be given in reduced
dosages
- dosage should also be reduced for drugs used for actions outside the CNS if
those drugs are capable of producing CNS toxicity as a side effect

Hepatic Metabolism
The drug metabolizing capacity of newborns is low.
- as a result, neonates are esp. sensitive to drugs that are eliminated by hepatic
metabolism
- The capacity of the liver to metabolized many drugs increases rapidly about 1
mo after birth and approaches adult levels a few months later.
- Complete maturation of liver by 1 yr.

Renal Excretion
Renal drug excretion is significantly reduced at birth.
- Renal blood flow, glomerular filtration and active tubular secretion are all low
during infancy.
- B/c ltd drug excreting capacity, drugs eliminated by renal excretion must be
given in reduced dosage.
- Adult levels reached by 1 yr.

Pharmacokinetics
Children 1 yr and older

– Metabolize drugs FASTER than adults


– Elevated until about 2 yrs old, then gradually declines
– b/c enhanced metabolism of drugs, an increase in dosage or reduction in
dosing interval may be needed for drugs that are eliminated by hepatic
metabolism

Adverse drug rxns

Like adults, pediatric patients are subject to adverse reactions when drug levels
rise too high.

– Age related effects are growth suppression (glucocorticoids), discoloration of


developing teeth (tetracyclines), kernicterus (condition marked by the
deposit of bile pigments in the nuclei of the brain and spinal cord and by
degeneration of nerve cells that occurs usually in infants as a part of the
syndrome of erythroblastosis fetalis )- (sulfonamides)

Dosage determination
The method of conversion is based on body surface area:

Approximate child dose= body surface area of child x adult dose/1.73 m2

This is an approximation!! Must monitor for + and – effects!


Promoting Adherence
parent and guardian essential.
- 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.

W/ young kids, spitting out, spills cause inaccurate dosing.