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10
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
6 groups:
As young patients grow older, they become more like adults physiologically and
more like adults w/regard to drug therapy
B/c we have insufficient drug info on peds, we have more difficulty w/ dosing,
pharmacokinetics, effects (therapeutic and adverse)
– Drug absorption
– Protein binding of drugs
– Exclusion of drugs from CNS by BBB
– Hepatic drug metabolism
– Renal drug excretion
Absorption
– 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
– 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
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
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
Like adults, pediatric patients are subject to adverse reactions when drug levels
rise too high.
Dosage determination
The method of conversion is based on body surface area: