Recent pharmacological advances in paediatric analgesics

Growth and development are two linked processes that distinguish children from adults. The use of size as the primary covariate during pharmacokinetic (PK) analyses allows exploration of the effects of age. Allometric scaling models have assisted understanding of the developmental clearance changes in common analgesic drugs such as paracetamol, morphine, tramadol and local anaesthetics agents. Single nucleotide polymorphisms (pharmacogenomics [PG]) and their impact on hepatic drug metabolism for opioids, tramadol, non-steroidal anti-inflammatory drugs (NSAIDs) and drug receptor responses are increasingly reported. Altered chemical structure or formulations of common analgesics alter pharmacodynamic (PD) effects enhancing safety and efficacy for NSAIDs by stereoselectivity and the addition of nitric oxide, for intravenous paracetamol by formulation and structural difference from propacetamol and for local anaesthetics through stereoselectivity. This article focuses upon recent data for analgesics used in paediatric pain management including paracetamol, NSAIDs, morphine, tramadol, amide local anaesthetics and ketamine. It centres on PK and clinical studies in neonates, infants and children. PG studies are acknowledged as potentially allowing individual drug therapy tailoring through a decrease in between-patient population variability, although the impact of PG in the very young is less certain. There are few data describing age-related PD changes in children despite recognition that the number, affinity and type of receptors or the availability of natural ligands changes with age.