Paediatric pharmacology Flashcards
What is the difference between the following?
- Premature baby
- Full term baby
- Neonate
- Infant
- Child
- Young adult
- Premature = born before 37 weeks
- Full term baby = born 37-42 weeks gestation
- Neonate = baby up to 4 weeks old
- Infant = baby up to 1 year old
- Child = 1-12 years old
- Young adult = teens upwards
Pharmacokinetics vs pharmacodynamics?
Pharmacokinetics = ADME (body effect on drug)
Pharmacodynamics = drug effect on body
What are factors which affect drug dose and response?
- Growth + development of organs
- Drug absorption - eg. oral, IM, SC
- Drug distribution
- Metabolism
- Excretion
What is the most common route for absorption?
Oral -> Gastrointestinal
How is gastrointestinal absorption different for neonates?
- Newborns have reduced gastric acid secretion (normalise at 3yo)
- Gastric emptying slower in neonates
- Intestinal motility + integrity affect extent of drug absorption
- Disorders of GI tract affect absorption of orally administered drugs eg. gastroschisis
Oral route is unpredictable!
For intramuscular absorption, the absorption from injection site can be erratic. It depends on what factors?
- Vascular perfusion
- Muscular contraction
- Muscle mass
- Avascular tissue
- Shock
Are intramuscular injections encouraged in children?
- In ill neonates muscle blood flow varies considerably - sepsis, hypotension
- Not suitable for large number of drugs
- In general IM injections are discouraged in children - can be distressing + painful
Why is there an enhanced effect of percutaneous absorbed drugs in neonates?
- They have decreased thickness of stratum corneum
- Increased skin hydration
- Increased SA
What impact do topically applied corticosteroids have on children?
Lead to significant systemic drug levels - cushingnoid symptoms
Also topical aminoglycosides can lead to permanent hearing loss.
What is the problem with rectal absorption?
Variation in rectal venous drainage leads to erratic absorption
When is rectal absorption useful?
Useful route in patients who are vomiting/NBM or in infants + young children who are reluctant to take oral medication.
But not always popular or convenient.
Describe intravenous administration
- 100% bioavailability - child receives full drug
- Very commonly used
- Problems - access + drug compatibilities (safe to give 2 drugs together?)
What things do we need to consider in drug distribution?
- Sizes of body water compartments
- Plasma protein binding capacity
- Degree of development of BBB
- Metabolic disturbances eg. acidosis
- Drug specificity for tissue receptor sites
What is the volume of body water like in children and adults?
Total body water higher in neonates and young infants and continues to decrease to 60% by 4 months and remains like that.
Their adipose tissue also has more water than lipid
What is needed to achieve steady state in regards to there being higher total body water in young infants?
- May require large loading doses on mg/kg basis to achieve steady state
- Maintenance doses depend on clearance
How is body fat different in neonates compared to adult?
- Body fat reduced in neonates
- Adipose tissue composition different
How is protein binding different in neonates?
- Plasma protein concenctrations are reduced in newborn
- Binding capacity of protein redcued -> inc free floating drug
- Less protein, more drug floating, inc plasma concentration
- So therepeautic levels in adults may be toxic in neonates
What is kernicterus (bilirubin) and how is it caused?
- Comp for protein binding site occurs between drugs + endogenous substances
- Drugs may displace bilirubin from binding sites -> kernicterus
- Kernicterus is a bilirubin-induced brain dysfunction
- Similarly, bilirubin may displace drugs such as phenytoin with a resultant inc in free fraction
What are other factors that affect protein binding in (older) children?
- Malnutrition - hypoalbuminaemia (low alb)
- Nephrotic syndrome
- Hepatic disease
- Kwashiorkor disease - low alb
How is the blood brain barrier different in newborns?
Functionalyl incomplete -> inc penetration of drugs to brain
What does rate of transfer of drugs depend on within the BBB?
- Lipid solubility
- Degree of ionisation of drug
- Acidosis
- Hypoxia
- Hypothermia
Generally, how is hepatic metabolism altered in neonates?
- Neonates have immature drug metabolising systems - enzymes + function
- Age at which enzyme processes reach adult values varies with the drug + pathway of metabolism
- Liver function changes rapidly after birth
Some elimination processes may be superior by late infancy or childhood
How is phase 1 reaction different in neonates?
- Hydroxylation (phase 1) deficient in term neonate, even more so in preterm however matures rapidly
How are phase 2 reactions different in neonates?
- Sulphation + methylation (ph 2) not significantly impaired at birth + similar to adults
- Glucoronidation (ph 2) significantly immature, reaches adult values by 6-18 months old
Describe a couple of drugs metabolised by glucoronidation and their risks
- Chloramphenicol - risk of “grey baby syndrome”
- Indomethacin - prolonged elimination + platelet dysfunction
How is paracetamol metabolised in children?
- Usually by glucoronidation
- Instead metabolised by sulphation in children
How is theophylline metabolised in children?
- Theophylline metabolised to caffeine in neonates which is an active metabolite
- Caffeine is better - easier to monitor (therapeutic index not narrow)
- Don’t have to worry about toxic effects
When does maturation of renal function occur?
In first few weeks of life
In neonates, which is more mature: glomerular filtration rate or tubular reabsorption?
Glomerular filtration rate -> clearance of renally excreted drugs primarily by GFR in first few weeks of life.
This significantly alters elimination rates for some drugs eg penicillins, gentamicin.
Therefore, dose of a drug which is safe + effective in first week may be inadequate in the third week.
What causes adverse drug reactions?
- May be due to immature liver function
- Preventing detoxification + excretion
- –> high free drug conc in plasma
- Toxic reaction occurs
Why are adverse drug reactions common in children?
- Infants more likely to exp unusual or idiosynchratic rxns than older children or adults
- There is lack of info concerning use of many drugs in this age group
- ALL ADRs SEEN IN YOUNG CHILDREN MUST BE REPORTED
Why are there high error rates (25%) in medication in paediatric units?
- Wrong dose calculation
- Misplacement of decimal point
- Wrong frequency of administration
- Wrong route of administration
