Paediatric pharmacology

Question 1

Learning outcome

Answer 1

• To be aware of differences in drug absorption in paediatric patients
• To understand principles of prescribing in children (including use of the BNFc)
• To know how medication pharmacodynamics changes with each phase of childhood
• To identify problems associated with paediatric prescribing

Question 2

Challenges in paediatric prescribing

Answer 2

• Lack of acute dosage data
• Lack of appropriate formulations
• Difficulty detecting ADR
• In utero exposure and transplacental transfer of drugs in post natal period
• Different pharmacodynamics and pharmacokinetics
• Breast fed infants affected by mothers medication
• Lack of patient information

Question 3

Key points in paediatric prescribing

Answer 3

• Keep it simple
• Is the therapy needed and what’s the expected effect
• Minimum length to be on medication
• Monitoring efficacy and ADRs

Question 4

Off label and unlicensed

Answer 4

• Off label → licensed for human but not for use in children below certage age
• Unlicensed → no license for human use in country

Question 5

Indications for off-label prescribing

Answer 5

• Formulation administered via route not intended → capsule to serum
• Medication used for an indication not intended
• Medication used at different dose
• Children below recommended age limit
• Medicines without a license

Question 6

Risks of off-label medications

Answer 6

• Increased risk of ADRs and avoidable death

Question 7

Prescribing in neonates and infants

Answer 7

• More sensitive to drugs than adults → organ system immaturity
• Higher risk of adverse drug reaction
• Greater individual variability

Question 8

Prescribing in early post-natal period

Answer 8

• Rapid growth
• Highly variable alterations in drug metabolism and elimination
• Lower tolerance to ADRs
• Higher incidence of therapeutic errors
  
  • Difficulty identifying efficacy and toxicity

Question 9

Prescribing in infancy

Answer 9

• Body weight gain and rapid changes to body water composition
• Alteration to bodyweight to surface ration

Question 10

Prescribing in young adults

Answer 10

• Increased metabolism and secretion
• Around 30% of prescribed medications off label

Question 11

Prescribing in adolescence

Answer 11

• Sexual development → major changes in body size and composition
• Psychological changes and peer pressure → smoking, alcohol and illicit drugs

Question 12

SSRIs

Answer 12

• Paroxetine
• Associated with x4 increase in suicide compared to placebo when treating depression
• Drug used off label

Question 13

Oral medications in paediatrics

Answer 13

• Reduced gastric acid and delayed gastric emptying
• Reduced bioavailability in drugs with high hepatic clearance and first pass metabolism
• Variability in drugs with enter-hepatic circulation → cyclosporin

Question 14

Percutaneous medications in paediatrics

Answer 14

• Enhanced in infants and children → especially damaged skin
  
  • Think steroids

Question 15

Rectal medications for paediatrics

Answer 15

• Those vomiting or unwilling to take oral medications
• Avoids first past metabolism
• Significant variability, few preparation and trauma

Question 16

Paediatric drug distribution

Answer 16

• Newborns → high extracellular fluid volume (45%)
• High variability in fat content with development

Question 17

Blood brain barrier in paediatrics

Answer 17

• Not fully developed
• Drugs and chemical have easy access to CNS
• High sensitivity to drugs → CNS dysfunction and toxicity

Question 18

Drug elimination in paediatrics

Answer 18

• Immature neonatal liver → slower hepatic elimination
• Longer time to reach steady state
  
  • Same process in kidneys

Question 19

Hepatic metabolism in paediatrics

Answer 19

• Very slow due to immaturity of metabolising enzymes
• Reduced oxidation and glucuronidation
• Interindividual differences in hepatic metabolism
• Rapid metabolic activity from 1 month with adult activity from age 1

Question 20

Metabolic disturbances in paediatrics

Answer 20

• Drug sensitivity increased by
  
  • Fever
  • Dehydration (lower hydration reserves)
  • Acidosis (decreased cellular penetration)