Pharmacology : Drug Distribution

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  • Created by: Sophie
  • Created on: 16-01-13 15:19
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  • Drug Distribution
    • Facts
      • Once absorbed from site of admin. into plasma, the drug is distributed throughout the body:
        • 1. Bulk flow in systemic circulation (~1 min)
        • 2. Drugs move into tissues + body fluids by; diffusion and carrier-mediated transport
    • Binding of drugs to plasma proteins
      • At therapeutic concentrations in plasma, many drugs exist mainly in bound form
      • The unbound drug is the pharmacologically active drug
      • The most important plasma protein is albumin
      • The amount of drug that is bound to protein depends on:
        • 1. The conc. of free drug
        • 2. The affinity of the binding sites
        • 3. The concentrationof protein
    • Drug interactions
      • Binding sites on plasma proteins may bind many diff. types of drug
        • Competition occurs between drugs
          • If 2 drugs compete in this way (A+B), admin of drug B can reduce the protein binding + hence increase plasma conc. of drug A
        • If 2 drugs compete in this way (A+B), admin of drug B can reduce the protein binding + hence increase plasma conc. of drug A
      • If a high % is bound then there's potential to be affected by drug interaction
        • If a high % is occupied then there's potential to cause drug interaction
    • In tissues
      • Drug targets are mosst often in tissues
      • Movement of drug from plasma into tissues involves same principles as drug absorption
        • Speed of drug movement depends on:
          • 1. Bl. flow
          • 2. Ability to cross tissue barriers
          • 3. pH partition effects
          • 4. Partition into body fat
      • Distribution of drug is not limited to target tissues
      • Drug may be higher in liver/kidney than target tissue
    • Volume of Distribution
      • The apparent volume of distribution (Vd): the volume of fluid required to contain the total amount, Q, of drug at the same conc as present in plasma, Cp
        • Vd = Q / Cp
        • Size of Vd suggests where the drug goes in the body
          • Varies from drug to drug
          • Tends to match a body fluid compartment
        • Total Body Water (TBF): ~0.5 l/kg
          • eg. paracetamol
        • Extracellular fluid (ECF): ~0.2 l/kg
          • eg. tubocuranine
        • Plasma compartment: ~ 0.05 l/kg
          • eg. aspririn
        • Vd > TBF indicates drug accumulates in specific compartments

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