↓
activity of microsomal enzymes responsible for Phase I (non-synthetic)reactions involved in metabolism of synthetic opioids. Activity reaches adult levels with a few days of birth.
Ability to for conjugates (Phase II, synthetic reactions), eg with glucuronide, does not approach adult levels until 6 months of age →
affects elimination of morphine
Elimination
Immature kidneys →
↓
GFR (~10% of adult) →
↓
renal clearance of drugs
↓
tubular secretion mechanisms
Proximal tubule secretion is important for elimination of conjugated drugs and reaches adult values by 7 months of age
Anaesthetic Drugs
Inhalational Agents
MAC lower in preterm infants than in term infants and increases with PCA
MAC
increases to maximum at 6 months of age then starts to decrease
Sevo is atypical. No change in MAC <
6 months. After 6 months, abrupt step down in MAC, following which it remains constant during childhood
Rate of rise in FA:FI is more rapid, due to 4 factors (listed in order of decreasing importance)
Greater alveolar ventilation in relation to FRC
Greater % cardiac output distributed to vessel rich group
Lower tissue/blood solubility
Lower blood/gas solubility
Intravenous Agents
↑
Sensitivity to barbiturates and opioids
Due to immaturity of BBB →
faster penetration and rise in conc
Also greater % CO to VRG
Greater sensitivity of respiratory centre to effects of opioids
Prolonged duration of action
↓
hepatic metabolism and renal excretion
Muscle Relaxants
NMJ 3 times more sensitive to NDMR but balanced by
Vol of distribution ↑
x 3 times (large ECF vol) →
Same dosing as adults!
However, prolonged elimination times →
↓
dose and frequency of top ups
Suxamethonium
Higher Vd but counteracted by lower levels of psuedocholinesterase
Dose double that of adults 2mg/kg
Duration of action 5 - 8 minutes, terminated by plasma cholinesterase
Hydrolysis slower in preterm infant (immature liver)
Due to actions on mus ACh recs in SA node, may →
bradycardia, asystole
Local Anaesthetics
Higher risk of toxicity
↓
protein binding to 𝛼1 acid glycoprotein →
↑
free fraction →
↑
toxicity