Lec 17- Paediatric drug use

Question 1

Terminology- what terms do we use to describe age

Answer 1

• Post conceptial age= gestational age and postnatal age
• Pre-term or premature= born <37 weeks
• 0-27 days= neonate
• 28 days-23 months= Infants & Toddler
• 2 years- 11 years= child
• 12 years- 16 or 18 years= Adolescent

Question 2

What changes occur in childhood that can influence medicines

Answer 2

• PK- ADME
• Pharmacodynamic

Question 3

Absorption- oral

Answer 3

• GIT- affects stability and ionisation of a drug
• Neonates- Increased pH (6-8)
  
  • Decreased absorption of acidic medicines
  • Small bile = less absorption of lipophillic
• Gastric emptying and intestinal motility influence absorption
• Absorption is erratic in newborn
  *

Question 4

Absorption- other

Answer 4

• IM injections
  
  • Rate and extent of absorption depends upon blood flow to the muscle
• PR- May be slow and unpredictable
• Percutaneous- absorption significantly greater than in adults
• Intraosseous (IO)
  
  • Injection into bone (Usually tibia)
  • Useful when can’t give via IV

Question 5

Distribution

Answer 5

• Water higher in children
  
  • Larger Vd= lower concentration= higher dose
• Fat higher in water
  
  • Lower Vd= higher concentration= lower dose

Question 6

IV fluid requirements

Answer 6

Question 7

Distribution- Protein binding

Answer 7

• Altered in neonates and young infants- reduced
  
  • Reduced quantity of total plasma proteins
  • This increases free fraction of drugs
  • Increases foetal albumin in neonates
  • Increases bilirubin and free fatty acids in neonates (Which are capable of displacing drugs)
• All leads to increased plasma levels of highly protein bound drugs (Phenytoin, furosemide, phenobarbitone)- less protein= more active in blood so reduce dose

Question 8

Metabolism

Answer 8

• Enzymes in liver, kidneys and GIT
• 2 stages: Phase I (primarily oxidation); Phase II (conjugation)
• Activity of CYP450 and glucuronosyltransferase reduce at birth

Question 9

Phase 1 metabolism

Answer 9

• Phenytoin (2C9 & 2C19)
  
  • Prolonged t_1/2 of ~75 hours in a pre-term neonate
  • 20 hours in term neonate during 1st week of life
  • 8 hours after 2^nd week
• Theophylline (1A2)
  
  • At term t_1/2 of 8-18 hours
  • Reducing to 3-4 hours by 48 week
• Phase 2 metabolism
  
  • Paracetamol- Sulphation main route of metabolism in neonates and early infancy
  • This changes to glucuronidation after several months

Question 10

A twist

Answer 10

• In the 1-9 year age group metabolic clearance is shown to be high than in adults
• Higher mg/Kg doses required for equivalent plasma levels
• Aminophylline
  
  • 1 month- 12 years 1mg/kg/hr
  • 12-18 years 500-700 mcg/kg/hr
  • According to theophyliine concentration

Question 11

Gentamicin dosing in children

Answer 11

• Elimination is almost completely by glomerular filtration of unchanged drug
• Clearance

Question 12

Can we use the Cockcroft and gault equation in children

Answer 12

• GFR (mL/min/1.73m²)= 40 x height (cm) / serum creatinine
  
  • For neonates= 30 x height (cm) / Serum creatinine
  • for accurate dosing

Question 13

Pharmacodynamic effects

Answer 13

• Talking about the interaction between drug and receptor
• Less known
• May explain increased hepatic toxicity seen in infants on sodium valporate

Question 14

Getting medicines into children only

Answer 14

• Can be challenging
• Tablets or capsules
  
  • Adult formulation
  • Lack of licensing in children for many liquids
• What can we do to tablets/capsules

Question 15

Getting medicines into children orally

Answer 15

• Often use specials
• Excipients used
  
  • Additives- e.g. colours numbers 100-181 and preservatives 200-290
  • Sweetening agents
    
    • Sucrose- Chewable tablets may contain >50% and liquids >85% sucrose
    • Sugar alcohol
    • Aspartame (aspartic acid and phenylalanine)

Question 16

Formulation issues- liquids

Answer 16

• Vehicle composition
  
  • Ethanol 2^nd most common after water
  • The U.S have set limits of 10% for children >12 years, 5% for 6-12 yrs & <0.5% <6 yrs
• Phenobarbitone elixir contains 38% alcohol
• Propylene glycol is used as a solvent in lipid-soluble oral, topical and I.V medicines (e.g. phenytoin and diazepam
  
  • Side effects: Osmotic laxative effects, contact dermatitis, serum hyperosmolality, lactic acidosis, seizures and cardiac arrhythmias in high dose long term

Question 17

Getting medicines into children alternative routes

Answer 17

• Suppositories
  
  • Uniformity of dose more uncertain
  • Splitting- lengthwise
• Patches
  
  • There are no transdermal patches available for paediatric use
    
    • Cut matrix or adhesive type patch
    • Cover reservoir patch

Question 18

Other considerations with medication choice in paediatrics

Answer 18

• Allergy status
  
  • E.g. penicillin
  • Ketogenic diets often used in complex epileptics
• Error potential
  
  • Complexity of calculations
    
    • May involve more than one step
  • Use of unlicensed medicines

Question 20

Medication Errors- case reports

Answer 20

Question 21

Ways to prevent errors in children

Answer 21

• Prescribing
  
  • Don’t prescribe if unfamiliar
  • Check and record on drug chart, C/I, allergies and interactions
  • Confirm correct weight used and add to drug chart
  • weight based dose should not exceed adult dose
  • Prescription must be legible

Question 22

Ways to prevent errors in children

Answer 22

• Calculations- Each step is written out and double-checked
• Administration
  
  • Nurse/clinical to check drug, dose and pt identity
  • Confirm unusual volumes with pa prescriber
  • Listen to pt and or care giver attentively and answer any questions
• Safe Hospital environment
  
  • Staffing, standardised equipment, no blame culture

Question 23

Incidence of ADR in paediatrics

Answer 23

• Cause of hospital admission 2.1%
  
  • 39.3% were life-threatening
• Overall incidence in hospitalised children 9.5%- 12.3% considered severe
• Outpatients ADRs seen in 1.5%

Question 24

Dosing information in paediatrics

Answer 24

• BNFc
  
  • National standard text
  • Info on use of a medicine in renal, liver, pregnancy or breast feeding within monograph
  • Some licensing information
• Alternative sources
  
  • Medicines for children
  • Lexi-comp
  • Neonatal formulary
  • Martindale

Question 25

Medication history and children

Answer 25

• Medicines reconsiliation is important in paediatrics
• Key information to establish
  
  • Regular medication
  • OTC neds
  • Allergies
  • Vaccinations/ Immunisation history