Distribution november 12.docx - DISTRIBUTION INFANT...

DISTRIBUTION
INFANT ANTI-BACTERIAL CASE STUDY
Purpose: To try and identify an effective management strategy for treating bacterial infections in premature infants
What they found
 Tetracycline had lower mortality rates when compared to sulfonamide-penicillin
 Sulfonamide was found to displace bilirubin on albumin in the blood, leaving bilirubin free in the blood
o As we have discussed in chemical toxicology, bilirubin can be fatal to infants as they do not have a
sophisticated blood-brain barrier
 This lead to kernicterus
o Unconjugated bilirubin crosses the blood brain barrier and deposits in the grey matter of the
brain
o This leads to cell signalling issues, developmental delays, and even death
BARRIERS IN DRUG MOVEMENT
Locations
 Blood-brain barrier
 Placental barrier
 Blood-testis barrier (not a “true” barrier)
Structure
 Tight intracellular junctions (decrease paracellular movement)
 Thick lipodial membranes
 Lack of pores
 Various metabolizing/degrading enzymes
Functions
 Stop/slow the free flow of compounds in/out of specific areas
 Control the influx and efflux of compounds
 Block absorption and favour elimination
BLOOD-BRAIN BARRIER

Structure
 Thick lipodial membrane (made of basement
layer, endothelial layer, and glial cells) that
separate the blood and cerebrospinal fluid
(CSF)
 Very tight junctions between endothelial
cells
o Limiting water soluble paracellular
diffusion
 Various efflux transporters that will push
compounds back out if they do happen to
diffuse through
o MRP transporter
 Low protein content
o Limit bound toxin transport
Function
 Protect the brain! Limit the influx/efflux of ions and compounds
 Mediated primarily by glial cells of which provide the third layer of protection
 Increase the diffusion distance between blood and CSF to make diffusion more difficult
 Glial cells and astrocytes secrete chemical factors
o Control permeability
o