What are the differences in the way children handle drugs in comparison to adults? What implications do these have?
Features
Implications
- Liver function is initially immature, with decreased hepatic enzyme function
- Drug metabolism may be slower leading to a longer duration of action (e.g. barbiturates and opioids)
- Renal blood flow and glomerular filtration rate are low in the neonate and young infant due to increased vascular resistance
- Reach adult levels between 1 and 2 years age
- Alters the pharmacokinetics of drugs, particularly renally excreted, requiring age related dose adjustment
- Less able to handle and excrete exogenous fluid and sodium loads – low sodium fluids often used in neonates
- Loop of Henle is short in newborns and tubular function is immature during first year
- Less able to reabsorb fluid and sodium resulting in production of dilute urine
- Hydrogen ion excretion, acid secretion & bicarbonate levels are lower
- Neonates and infants prone to dehydration as unable to produce concentrated urine to withstand fluid deprivation
- Prone to develop severe metabolic acidosis due to difficulties handling acid –base balance
- Total amount of water is 75-80 % of body weight in childhood, 60 % in adults
- There is a larger proportion of extra cellular fluid in children (40% body weight as compared to 20% in the adult)
- Alters the pharmacokinetics of drugs
- Blood brain barrier is poorly formed
- Drugs such as barbiturates, opioids, antibiotics and bilirubin cross the blood brain barrier easily causing a prolonged and variable duration of action