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This carriers carriers a albumin major blood binding

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Unformatted text preview: blood KNOW THIS CARRIERS Carriers a. ALBUMIN –major blood binding protein (Barbituates, Ca2+, Vitamin C) binds to most compounds that we will discuss more then 1 binding site b. Erythrocytes- (RBC’s carry O2 CO also have negative effect ) can remove waste (CO2) biggest competition is CO CO has a higher affinity for erythrocytes then O2 c. Lipoproteins- (LDL, HDL steroid lipo proteins hormones, fatty vitamins) high and low densitysteroids can also carry and fatty xenobiotics are carried by this d. Globulins- not as abundant (alpha, beta carry acidic and basic toxicants) know different kinds of BBP and generally what they carry hemoglobins can also carry metals Blood Binding Proteins Various non-covalent forces in binding pocket will determine selectivity and binding affinity proteins also have non-polar amino acids - Hydrophobic interactions effect may associate - Van der Waals forces electronicchargeswith compounds with certain - Hydrogen Bonding Binding Site Competition Displaced toxin Free form e.g. aspirin - phenylbutazone toxicity (two NSAIDs, compete for same site see increased concentration of one) non-sterol anti-inflammatory drugs (NASIDs) free compound replaces bound compound, and now higher concentration of replaced bound compound toxicosis can occur Effect of Binding a) Toxic effects i.e. Pb = 99% bound b) Elimination increases residency effect causes more toxic response ALWAYS REMEMBER EQUILIBRIUMS!! never all or nothing, if they stay in blood for longer, equilibirum gets changed more and more can enter tissues Chemical Binding and Filtration Not Available Chemical Available spaces between kindeys aren’t big enough to excert BBP Kidney Longer residency time = toxicity As free chemical is eliminated, more dissociates from protein. Distribution: Chemical transport in the blood 1. BINDING SITE COMPETITION Displacing a bound toxicant free toxicant (e.g. phenylbutazone displaces acts as a toxicant warfarin) warfrin gets replaces and toxicity Increased blood concentrations = toxicosis! also acts as a theraputic 2. INCREASED ‘RESIDENT TIME’ Increased binding decreased free toxicant conc. decreased elimination (e.g. Pb2+ long residency time from high binding ) Blood Protein Binding of Chlorofibric Acid Species Plasma Protein binding (%) Half-Life (hrs) Man 97 21 Rat 75 6 Mouse 45 2 Infant Anti-bacterial Case study 1958 study to try and find a prophylactic anti-bacterial strategy to combat infections in premature infants. Tried two...
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