DR SIMON ATTARD MONTALTO
Variable issues in children:
access and delivery
absorption
volume of distribution
metabolism
clearance
These impact on:
efficacy
toxicity, side effects
interactions
Other issues:
licensing
research studies/data
costs
Influence of age
GI absorption: gastric pH rapidly after birth, slowly later
gastric emptying irregular
GI motility variable, steadies with age
GI motility affected by type/volume feed
GI flora
Enzyme activity:pancreatic increases with age
gall bladder activity/contraction
hepatic enzyme efficiency
GI flora
Administration
oral route:
liquid better than tablets
palatability & compliance
bioavailability
i.v. route:
problems with access
infusion or bolus (volume, rate, flush)
dead space, bore of cannulae
‘piggy-backing’, infusion drug interactions
infection risk,
extravasation
bioavailability depends on perfusion
i.m. route:
pain
bioavailability unreliable
skin:
large surface area (X3)
absorption of toxins
bioavailability dependent on hydration
lungs:
few agents
ideal when possible
local irritation/bleeding/flooding
Depends on:
volume of distribution
binding to plasma proteins (e.g albumin)
Drug metabolism
Depends on:
liver function
also renal, intestine, lung, adrenal, skin function
affects dosage calculation with age
Depends on:
renal tubular and glomerular function
e.g GFR slow <34wks; 2-4ml/min at birth; 8-20ml/min by 3 days; gradually increases to adult value by 5 months
Pharmokinetics
‘time course of drug in the body’
most linear kinetics
some saturation (zero order) kinetics, e.g phenytoin, salicylates, alcohol
Drug pharmokinetics is a factor of the following:
bioavailability
absorption
volume of distribution
elimination (t1/2)
clearance (total Cl depends on Clrenal, Clhepatic, etc)
perfusion, blood flow
Individualisation
great variability despite standardisation
genetic factors, intercurrent pathology
Target levels:
problematic in children
use only as guide
balance clinical effect against toxicity
drugs with clear response/toxicity ratio timing of sampling may be crucial
1. aware of indications, efficacy, side effects
2. aware of drug interactions
3. prescibe by weight, age, surface area - no guesstimates
4. write/prescribe clearly (legally inexcusable)
5. consult if in doubt
6. safe practice: check 5Ds: drug, dose, dilution, date, dual
7. aware of costs/accountability (generics vs parent drug)