Gastrointestinal absorption of drugs in newborn is implicated as:
they have less gastric acid which is ph~7..
give 3 other reasons
- peristalisis is reduced in first 6months
- reduced production of bile
- GI disorders e.g. gastroschisis, NEC that reduce absorption so need to deliver via TPN
How will absorption of acid labile medicines e.g. penicilin be affected by the gastric acid in a newborn?
As the gastric acid is more alkaline (ph 7) you will get more absorption
IV for drugs in babies is commonly used as it has 100% bioavailability, give 2 disadv of this method of administration:
- difficult line access
- drug compatibility
- infection risk
- longer hospital stay, $$$
Why is intramuscular administration of drugs in babies discouraged?
- absorption form injection site is erratic/variable
- depends on vascular perfusion there, muscle mass and contraction
- too painful
In what 2 pathologies is intramuscular administration of drugs in babies esp. discouraged due to the variable blood flow?
Hypotension
Sepsis
Caution should be taken with percutaneous administration of drugs into the skin of neonates in terms of absorption. Why?
- thinner s.corneum
- increased skin hydration
- larger SA so enhanced absorption
What are the risks associated with the following drugs admisistered percutaneously in neonates?
- topical corticosteroids
- topical aminoglycosides
- Corticosteroids may reach high systemic levels –> Cushingoid symptoms
- Aminoglycosides can lead to hearing loss
Rectal administration of drugs to babies/children is useful in 2 instances in particular…when? What can lead to erratic absorption here?
- vomiting/nil by mouth patients
- children reluctant to take orally
- variation in rectal venous drainage
Vd is the degree to which a drug is distributed in….. rather than…..
distributed in…..body tissue rather than…..plasma
Suggest 3 `things that affect the degree of drug distribution (once within circulation) out of plasma.
- size of body water compartments
- how much drug binds to p.proteins
- degree of development of BBB
- metabolic disturbances e.g acidosis
- specificity of drug to receptor sites
How does total body water and adipose % in neonates compare to adults? Hence water-soluble drug distribution…?
- higher body water (92 vs 60%) and less adipose in neonates
- higher loading doses of water-soluble drug needed to reach steady state
How does the fact that neonates have less plasma protein with lower binding affinities affect Vd?
-less bound drug so more free fraction so more distribution out from plasma
The drug phenytoin is 98% protein bound, how does it cause kernicterus + long-term neuro damage in neonates?
- phenytoin can displace bilirubin
- more free bilirubin which can cross BBB –> kernicterus
Hypoalbuminea can affect protein binding. Suggest 2 conditions this can occur with.
- malnutrition
- sepsis
- nephrotic syndrome
- hepatic disease
What is different about the BBB in neonates? What 2 factors determine the rate of drug transfer to the CNS?
- BBB is functionally incomplete so more enters CNS
- lipid solubility and ionisation of drug affect it
How is hepatic metabolism of drugs in neonates?
Phase I hydroxylation
Phase II Sulfation/Methylation/Glucoronidation
Immature as enzyme functioning esp CYP has delayed maturity (phase I)
Phase II Sulfation/Methylation = normla
Glucoronidation = immature until ~1yr
What syndrome can the antibiotic chloramphenicol or idomethacin cause in a baby due to immature hepatic metabolism?
Grey Baby Syndrome
Nephrogenesis is from wk9-34 gestation but renal function is still immature at birth. In children what can further compromise function, give 2 e.g.s.
- sepsis
- dehydration
- nephrotoxic drugs
Suggest why ADRs are more common in neonates.
- lack of clinical trial data
- immature liver function–>lack of detoxification and excretion so drug accumulates
What is dosage in paedatric units based on?
-weight/SA
The myometrium has 3 smooth muscle layers, what are the fibre orientations?
- outer: longitudinal fibres
- middle: figure of 8 fibres
- inner: circular fibres
How does the myometrrium sm organisation act like a ligature preventing blood loss in birth?
- contraction of the fibres increases the uterine pressure
- forces the contents towards the cervix
The myometrium is spontaneously active/myogenic. What modulates contractions? (increases/decreases?)
- NTs influence
- Oestrogen increases contractions
- Progesterone inhibits activity
-In the non-pregnant uterus why do they experience weak contractions early in the MC and strong contractions during menstruation? (horomones..)
- progesterone starts high then decreases (inhibitory)
- prostoglandins increases at menstuation
