Paediatric pharmacology

• 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 = ADME (body effect on drug) Pharmacodynamics = drug effect on body

• Growth + development of organs • Drug absorption - eg. oral, IM, SC • Drug distribution • Metabolism • Excretion

Oral -> Gastrointestinal

• 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!

• Vascular perfusion • Muscular contraction • Muscle mass • Avascular tissue • Shock

• 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

• They have decreased thickness of stratum corneum • Increased skin hydration • Increased SA

Lead to significant systemic drug levels - cushingnoid symptoms Also topical aminoglycosides can lead to permanent hearing loss.

Variation in rectal venous drainage leads to erratic absorption

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.

• 100% bioavailability - child receives full drug • Very commonly used • Problems - access + drug compatibilities (safe to give 2 drugs together?)

• Sizes of body water compartments • Plasma protein binding capacity • Degree of development of BBB • Metabolic disturbances eg. acidosis • Drug specificity for tissue receptor sites

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

• May require large loading doses on mg/kg basis to achieve steady state • Maintenance doses depend on clearance

• Body fat reduced in neonates • Adipose tissue composition different

• 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

• 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

• Malnutrition - hypoalbuminaemia (low alb) • Nephrotic syndrome • Hepatic disease • Kwashiorkor disease - low alb

Functionalyl incomplete -> inc penetration of drugs to brain

• Lipid solubility • Degree of ionisation of drug • Acidosis • Hypoxia • Hypothermia

• 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

• Hydroxylation (phase 1) deficient in term neonate, even more so in preterm however matures rapidly

• 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