Patient factors impacting on prescribing, such as adverse drug reactions, age, and pregnancy

Overview

Age and pregnancy status substantially modify both pharmacokinetics (altered absorption, distribution, metabolism, excretion) and pharmacodynamics (altered receptor sensitivity), requiring specific dose adjustment and drug selection considerations distinct from standard adult, non-pregnant dosing references
Relevant across paediatric, older adult, and pregnancy-related prescribing, each representing populations frequently underrepresented in the clinical trials underlying standard dosing recommendations

Paediatric patients have immature hepatic/renal clearance mechanisms in early infancy (requiring careful, often weight-based dosing) that mature over the following months to years; older adults typically have reduced renal/hepatic clearance, altered body composition (reduced lean mass, relatively increased fat mass affecting distribution of lipophilic drugs), and often increased receptor sensitivity to certain drug classes (e.g. CNS depressants) - together increasing both drug exposure and sensitivity at a given dose compared with younger adults
Pregnancy increases plasma volume and renal clearance for many drugs (sometimes requiring higher, not lower, doses to maintain therapeutic levels) while simultaneously requiring fetal safety consideration

Weight-based or specifically validated paediatric dosing (not simple fractional adult dosing) should be used given the non-linear relationship between age/weight and clearance maturation
"Start low, go slow" dose titration is a reasonable general principle in older adults given increased sensitivity and reduced clearance, though should not be applied so cautiously that adequate treatment is withheld

Age-specific and pregnancy-specific dosing references should be consulted rather than extrapolating from standard adult dosing, given the substantial pharmacokinetic/pharmacodynamic differences in these populations
Regular reassessment of dosing appropriateness as a paediatric patient grows/matures, or as an older adult's organ function or frailty status changes over time

Neonatal/infant immature drug clearance, older adult increased CNS depressant sensitivity, pregnancy-associated increased renal clearance sometimes requiring dose increase (not decrease), weight-based paediatric dosing principles

Pregnancy increases renal clearance for many drugs, meaning some medications may actually require a higher, not lower, dose to maintain therapeutic effect during pregnancy - this is a frequently overlooked point given the natural clinical instinct toward caution and dose reduction in pregnancy, which is the correct approach for fetal safety reasons but not necessarily for maternal pharmacokinetic reasons

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