Principles Lec 4 2013

Tried two formulations tetracyline and

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Unformatted text preview: formulations e and sulfonamidepenecillin mixture had a lower mortality rate than did the sulfonamide-penecillin mixture used mortailty as an endpoint looked at what caused death, if it was bacterial or something else babies were dying to not bacteria but condition called kernicterus yellowing of body means billrubin is not being removed properly Billirubin natural product in the body when hemoglobin is broken down, billirubin is made The sulfonamide displaced bound billirubin on protein carrier albumin. It had a higher affinity to the protein and billirubin was displaced Billirubin is the normal breakdown product of heme catabolism (RBC, O2 carrier) in spleen Normally, sent to the liver bound to albumin In liver, billirubin is conjugated and eliminated Albumin Albumin Billirubin Binding Pocket Binding Pocket Free Billirubin in Blood stream Sulfonamide antibiotic would bind to albumin, kick off billrubin, got passed BBB, because babies BBB was [blood] of billrubin increased not fully developed got passed BBB, and got to brain, deposited in gray matter in brain caused degradation of brain matter babies would die of seziures Kernicterus Unconjugated billirubin is able to cross the infant BBB because it is yet to be fully developed Billirubin deposited in the cells of the grey matter and causes a condition known as kernicterus Involves apoptosis and degradation of neurons and glial cells Exact mechanism unclear, could involve inflammatory responses by neurons. Symptoms include lethargy, hypertonia, seizures, death BARRIERS TO DRUG ENTRANCE Highly protected locations in the body possess barriers to control their environments. Location: 1) Blood Brain Barrier (BBB) 2) Blood Placenta – 6 layers of cells, enzyme protection all these are an extra layer of protection 3) Blood Testis they have no paracellular diffusion Remember: a. Tight intracellular junction b. No “pores” c. Thick lipoidal barriers d. Degrading enzymes (placenta) size of compound becomes an issue have a ticker lipoidal, meaning there is longer a compound has to travel designed to keep compounds out to area they are protecting so compound re-enters blood steam and body should be able to remove the compound before it comes back Significance: Slow rate of distribution to these compartments elimination. allows for time for Blood Brain Barrier Between blood and Cerebral Spinal Fluid (CSF) can get some diffusion Selectivity of chemicals crossing the BBB: 1. specific transporters (Pr...
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This document was uploaded on 04/07/2014.

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