What’s a Pre-term baby?
What’s a Full-term baby?
What’s a Neonate?
What’s an Infant?
What’s a Child?
What is Drug dose and response affected by? What does this stand for?
- <37 weeks
- 37-42 weeks
- Up to 4 weeks
- Up to 1yr
- 1-12yrs
- ADME - Absorption, Distribution, Metabolism, Excretion
ABSORPTION:
Oral:
What are the properties of the gut that affect drug absorption in a Neonate?
Intravenous:
Why is this so commonly used?
What does it put one at risk of?
Why is it a difficult route at times?
Intramuscular:
What is absorption based on?
→ What are these like in Premature babies?
Percutaneous:
Why are Topical corticosteroids avoided with Neonates?
Rectal:
When is this route used?
- • High Gastric PH at birth due to Underdeveloped gastric mucosa (= ↓Acid secretion)
• ↑Acid-labile drug absorption e.g. Penicillin
• ↓Peristalsis and Bile production
• GIT disorders affect absorption
- 100% Bioavailability
- Infection
- Difficulties in line access (needle insertion) and drug compatibilities
- Muscle’s Mass, Perfusion, and Contractions
- Mass and Perfusion are Low, and Contractions are inefficient
- Can cause significant systemic effects as they have a large surface area : body weight ratio
- If Oral/IV is unavailable, They refuse oral medication, Vomiting
DISTRIBUTION:
It’s affected by:
1. Body composition - What’s it like in Neonates?
→ How does this affect the drug doses given? Why?
- Plasma protein binding - What’s it like in Neonates?
→ What conditions affect protein binding? How?
→ How can this be dangerous? - BBB development - What’s it like in Neonates?
→ What affects its permeability?
- Higher total body water and Lower body fat
→ Requires larger initial doses to achieve the target serum concentration as the drug can distribute into the extracellular water - Reduced plasma protein conc. and binding affinity
→ Malnutrition, Nephrotic syndrome, Sepsis, Hepatic disease, which all cause LOW ALBUMIN
→ There’s competition for binding sites by endogenous compounds, which can displace protein-bound drugs = ↑Free drug = Toxicity - Functionally incomplete
→ Acidosis, Hypoxia, and Hypothermia
METABOLISM:
Where does it take place? What’s this like in Neonates?
Phase I - What is it? What occurs here?
→ What’s it like in Neonates?
Phase I - What is it? What occurs here?
→ What’s it like in Neonates?
- Liver - Underdeveloped and matures rapidly after birth
- Hydroxylation - Makes drug more lipid-soluble to enhance renal excretion
→ Deficient in neonates and worse in premature babies due to immaturity of required enzymes - Sulphation, Methylation, and Glucuronidation - Makes drug more water-soluble
→ Glucuronidation very immature in neonates
EXCRETION:
What is Renal function in children affected by?
What has to be monitored to check renal function?
- Sepsis, Dehydration, and Nephrotoxic drugs
- Serum Creatinine, eGFR, and Urine output
ADVERSE DRUG REACTIONS:
In Neonates, why can there easily be an adverse drug reaction?
Immature liver function prevents detoxification and excretion = Accumulation of drug in blood
