Paediatrics Flashcards
Why is the intramuscular route usually avoided in children?
Children have low muscle mass and muscle is poorly perfused in infants therefore good concentrations of drugs are unlikely to be reached.
When is the intramuscular route used to administer drugs in children and why?
Vitamin K is administered as an intramuscular injection immediately in newborns to prevent haemorrhagic disease. Acts like a depot medicine over the first few weeks of life.
Immunisations are also administered intramuscularly.
How does topical (percutaneous) route of administration differ in children in comparison to adults?
Topical drugs are much more likely to be absorbed readily in infants and young children due to immature epidermal barrier, increased skin hydration and a higher surface are to body weight ratio.
TRUE or FALSE:
Infants have a greater Vd than adults?
True
How does the relationship between Vd and dosing of drugs related in infants?
Due to increased Vd in infants, doses of drugs which are distributed in the extra-cellular fluid and/or total body water will need to be INCREASED.
e.g theophylline (distributes in ECF) or gentamicin (distributes in TBW) - therefore doses of these drugs are higher in infants than in adults.
Which factors affect how a drug is distributed in the body?
1) water to body fat composition
2) how protein bound a drug is
A neonate needs phenytoin to control their seizures. What therapeutic range is optimal for neonates?
6-15mg/L
normal range in children and adults is 10-20mg/L
Phenytoin is highly protein bound.
How does plasma protein concentration differ in children in comparison to adults?
Neonates have a lower albumin and total protein concentration. There is also increase competition of binding sites from high levels of bilirubin and free fatty acids which bind to serum albumin and proteins seen in neonates and infants. - this further increases the concentration of ‘free’ drug in the blood plasma.
What is the primary organ for drug metabolism?
liver
How does the liver metabolise drugs?
Two ways liver metabolises drugs:
1) hepatic phase 1 reaction
2) hepatic phase 2 reaction
What is hepatic phase 1 reaction?
Includes:
Oxidation - most common; CYP450 enzymes catalyse the reaction; most metabolites are still active after undergoing oxidation
Reduction
Hydrolysis
What is hepatic phase 2 reaction?
Involves conjugation - addition of an ionised group to the drug molecule or metabolite. The groups can include acetyl, methyl, gluthathione, glucuronic acid or sulphate conjugates - allows drug to become more water soluble to aid excretion.
How does drug metabolism differ in children?
Ability for the liver to undergo phase 1 or phase 2 metabolic reactions is premature.
Hepatic phase 1 reactions - ability for liver to undergo matures over the first few months of life. Adult levels reached at 6 months
Hepatic phase 2 reactions - acetylation or glucuronidation: levels reach adult stage around 3 years old
sulphate or glycine conjugation - levels at birth similar to adult levels
What impact does the immaturity of hepatic metabolism have in infants?
May lead to extended half-lives of hydroxylated* drugs
* hydroxylated drugs - undergone hepatic phase 1 reaction - form of oxidation reaction
e.g diazepam
Why should sodium valproate be used in caution in children, especially in those who are under three years of age?
Hepatotoxicity has been associated with sodium valporoate use in children.
