Prescribing for children

• absorption
  • oral 
    • developmental changes in surfaces of gut, GI motility and intraluminal pH alter rate and extent of absortion
    • slower gastric emptying for first 6-8 months
    • first pass metabolism increased for some drugs
  • IM
    • absorption erratic due to reduced muscle mass and variabilty of blood flow to/from site
  • percutaneous
    • increases the younger the pt because of thinner stratum corneum and increased skin hydration

• water soluble drugs
  • higher volume of distribution thus need higher dose/kg compared to adults for some drugs (e.g. gentamicin)
    • younger children have greater % of body weight as water/ less as fat (prem baby= 85%:1% whilst adult (60%:20%)
• protein bound drugs
  • reduced plasma proteins in neonates thus get reduced plasma-protein binding and a  get greater free conc of certain drugs (e.g. morphine, phenytoin, diazepam)
  • sulphonamides displace bilirubin from albumin resulting in worse neonatal jaundice (possible kernicterus)

• presence and activity of heaptic enzyme pathways vary in neonates and infants
  • most phase 1 enzymes appear AFTER birth but mature rapidly
    • e.g. in a preterm baby half-life of caffeine is 20-36 hours (use for apnea of prematurity)
    • by 1 month caffeine is of little use due to rapid incr in metabolism
  • phase 2 enzyme development is less well understood
    • morphine shows some conjugation at 24 weeks gestation but quadruples by 27-40weeks (thus need greater doses for pain relief)

NB hepatic metabolism phases:

• Phase 1: oxidation/reduction/hydrolisis of drug (oxidation catalysed by cytochrome P450 enzymes)
• Phase 2: conjugation of metabolite 
  • an ion group (glutathione, methyl or acetyl) is added- increases water solubility for excretion and decr pharmacological activity
    

• GFR and renal function are immature- reach adult values at 6 months
  • GFR in neonate is 30-40% of that of an adult
  • renally excreted drugs (e.g. gentamicin) therefore accumulated so need longer dosing intervals and monitoring

• Prem baby
  • <36 weeks gestation
• Neonate/newborn
  • 0 to 27 days
• Infant
  • 28 days to 23 months
• Child
  • 2 to 11 years
• Adolescent
  • 12 to 16/18 years

• approximate through formulas (e.g. (child body SA/adult body SA) x adults dose)
  • NOT reliable for pre-termneonates and infants
• base on:
  • age banding
    • usually for low therapeutic index drugs 
    • e.g. paractemaol, amoxacillin
  • weight (mg/kg)
    • NB childhood obesity- don't exceed adult dose when going by weight
  • body surface area (mg/m^2)
    • for narrow therapeutic index drugs
    • e.g. chemotherapy, immunosuppression
• over 12 years:
  • often clasify as adults for dosing
  • but need to acknowledge may be prepubescent (not at adult height/weight)
• in emergency:
  • Broselow tape
  • reference documents

• oral
  • liquids (syrups, suspensions) better tolerated than tablets
  • NB suspensions should be shaken before use
  • NB don't add to feed- may interact or not be fully taken
• IV better tolerated than IM
  • IM discouraged in neonates and young children due lack of suitable muscle and unpredictable absorption
• rectal
  • if oral not tolerated, esp in emergency (e.g. rectal diazepam)
• inhalation
• special routes:
  • intraosseus (IO)
    • via bone marrow b/c highly vascularised
    • esp in emergency
  • buccal
    • non-invasive
    • e.g. buccal midazolam

• IV chloramphenicol
  • grey baby syndrome
  • a/e in neonates
  • cyanosis, grey skin colour, decr BP, CV collapse
• aspirin
  • Reye's syndrome
  • acute encephalopathy
  • mitochondrial damage leading to rash, vomiting, liver damage
• tetracycline
  • affects growing teeth and bone
  • discolouration of teeth and growth stunting

NB try to avoid school time dosing (compliance and practicality issues)