Pharmacology in Paediatrics

Question 1

Summarise the bioavailability and the time to peak serum concentration of the various routes of administration of midazolam

Answer 1

Intravenous: 5 minutes (bioavailability 100%)
Intramuscular: 15 minutes (bioavailability 87%)
Rectal: 30 minutes (bioavailability 18%)
Oral: 53 minutes (although onset is in 10 minutes, bioavailability 27%)

Question 1

By what age does morphine metabolism reach adult levels in children. state the metabolic enzyme and the metabolites

Answer 1

By 6 months metabolism by UDP to M3G and M6G approaches 80% adult levels

Usually by 9 months - metabolism = adult levels

Enzyme:
Hepatic glucuronidation by uridine 5′-diphospho-glucuronosyltransferase (UGT) phase II enzymes.

Metabolites:
Morphine-3-glucuronide
Morphine-6-glucuronide

Question 2

What is the dose of adrenalin for a depressed neonate

Answer 2

0.01 - 0.03 mg/kg IV

0.2 mg/kg down ETT

Question 3

Describe the use of dexmedetomidine as a pre-medication in paediatric anaesthesia

Answer 3

Central alpha 2 adrenergic receptor agonist with analgaesic and sedative properties.

Minimal respiratory depression

Possible hypotension and bradycardia

Dose:
- IV 1 ug/kg
- Intranasal 1 ug/kg

Onset: 30 - 45 minutes
Duration: 85 minutes

Benefits
1. Smoother emergence
2. No resp depression
3. Anxiolysis and analgaesia
4. Minimal risk of paradoxical reactions

Question 4

What are the reasons for altered pharmacokinetics in the paediatric population

Answer 4

1. Variable and altered body composition
   - More TBW (75 infant: 65 Adult)
   - Less muscle
2. Immature liver metabolism (decrease bep. blood flow and enzyme activity)
3. Immature Renal excretion (decrease GFR and Tubular fxn)

Question 5

How is plasma protein binding affected in infants and which drugs does this affect?

Answer 5

Decreased protein binding
–> Increased free fraction of protein bound drugs
1. Bupivacaine
2. Thiopental
3. Antibiotics

Question 6

Why do Children require higher doses of propofol and thiopental

Answer 6

Increased volume of distribution of both of these drugs.

Question 7

What is the dose of succinylcholine in infants and why is this. How does the onset of of action of sux differ

Answer 7

Adult: 1mg/kg
Infant: 2mg/kg
Neonate: 3mg/kg

Paeds:
Increased volume of distribution of succinylcholine

Onset of sux is faster due to faster circulation time

Question 8

How do pharmacokinetics of NDMR differ in paeds

Answer 8

NDMR have a longer duration of action due to immature liver metabolism

Question 9

How should ketamine and infants be dosed with ketamine

Answer 9

Neonates and infants are resistant to the hypnotic effects of ketamine requiring slightly increased doses

Question 10

Why are infants and neonates more sensitive to opioids

Answer 10

Postulated mechanisms
1. Reduced metabolism
2. Easier entry into CNS with immature BBB
3. Increased sensitivity of respiratory centers

Question 11

how can an infant being sedated with dexmedetomidine have an unchanged BP and simultaneously a decreased Cardiac Output

Answer 11

Dex can cause peripheral vasoconstriction with increased SVR. Simultaneously Dex leads to reduced HR. As CO = SV X HR and BP = CO x SVR, it can be demonstrated that an infant might have maintained BP despite reduced CO during a dex infusion

Question 12

Discuss the pharmacodynamic and pharmacokinetic differences of remifentanil in paeds vs adults

Answer 12

Remifentanil
- It is the only opioid that is cleared faster in infants than in adults
- Clearance slows down with increasing age
- elimination half time is 3 - 8 minutes

The volume of distribution is higher and therefore a higher infusion rate is required for the same clinical effect versus adults

Remifentanil induced bradycardia is more common in infants vs adults