Distribution november 12.docx - DISTRIBUTION INFANT ANTI-BACTERIAL CASE STUDY Purpose To try and identify an effective management strategy for treating

Distribution november 12.docx - DISTRIBUTION INFANT...

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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
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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
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