Lecture-5 - Protein binding and pharmacological actions...

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Protein binding and pharmacological actions Only free drug (unbound) can reach its sites of action to exert a pharmacological effect. Binding to plasma proteins decreases the maximum intensity of action of a single dose of a drug because it lowers peak free drug concentrations achieved at the sites of action. Binding to plasma proteins also slows elimination of the drug by glomerular filtration in the kidney, or metabolism by the liver.
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Clinically-important aspects of plasma protein binding 1. When the free drug concentration is lower, pharmacological activity is decreased and drug clearance rates are decreased. 2. One highly protein-bound drug may be competitively displaced by another, increasing the pharmacological activity and elimination rate of the displaced drug. 3. Endogenous substances with high affinities for protein binding sites (eg., bilirubin , fatty acids ) may also displace a highly bound drug. 4. In disease states characterized by hypoalbuminenia (eg. in hepatic failure or nephrotic syndrome ), the percentage of drug in the unbound state will increase.
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Drug distribution following rapid i.v. injection Three stages of drug concentrations following i.v. administration of drug. For the first two or three circulation times through the body, the drug will be distributed through the circulation as a bolus. There is a danger of toxicity if the drug has a narrow margin of safety and injection is too rapid (eg. thiopental and respiratory depression).
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Drug redistribution in tissues Different tissues have different blood perfusion rates. Thus drugs in different tissues reach equilibrium (with plasma free drug concentrations) at different rates. The uptake and distribution of a drug such as halothane takes place in three phases. First there is a rapid uptake phase where drug is taken up into the vessel-rich group ( VRG ) of tissues such as the brain , heart and liver . A second slower phase involves drug uptake into the muscle group ( MG ) of tissues and lastly drug is taken up into the vessel-poor group ( VPG ) of tissues such as fat , skin , bone , ligaments and teeth . Rates of decline of drug levels in tissues follows this same order.
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Drug Biotransformation Drug biotransformation refers to the chemical transformation of a xenobiotic within a living organism, usually by enzyme-catalyzed reactions. Potential consequences of drug biotransformation reactions
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This note was uploaded on 11/04/2009 for the course BIO 365D taught by Professor Mihic during the Spring '08 term at University of Texas.

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Lecture-5 - Protein binding and pharmacological actions...

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