Pharmacology : Drug Absorption

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  • Created by: Sophie
  • Created on: 16-01-13 14:53
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  • Drug Absorption
    • Facts
      • The  movement of a drug from the site of admin, into plasma
      • Drugs must cross one or more biological barriers eg cell membranes
        • 4 main ways they cross cell membrane:
          • Diffusion through lipid; Diffusion through aquaporins; Solute carrier, membrane transporter; Pinocytosis
          • Diffusion through lipids + carrier-mediated transport are important
          • Aquaporins are too small to allow drug molecules through
      • Drug molecules move around the body in 2 ways:
        • Bulk flow
        • Diffusion
    • Drug Diffusion
      • Drugs diffuse through biological membranes along a conc. gradient
        • 1. Membranes are predominantly lipids
          • 2. Lipids are non-polar solvents
            • 3. Non-polar solvents dissolve non-polar substances
              • 4. Non-polar substances cross membranes easily
      • Close correlation between lipid solubility and the permeability of the cell membrane to diff. substances
    • Lipid Solubility of Drug
      • Degree of lipid solubility varies with chemical composition of drug
      • Solubility measured by oil-water partition coefficient
    • pH and ionisation
      • May drugs are weak acids or bases + so exist in their ionised/ unionised form
        • Ionised molecules have very low lipid solubility so cannot cross membrane
        • Unionised, uncharged molecules; their lipid solubility depends on chemical nature
          • Mostly lipid soluble
      • Degree of ionisation can be measured using Henderson- Hasselbach equation
        • For a weak base:
          • BH+ <--> B + H+
            • pKa = pH + log10 (BH+/B)
    • Effects of drug ionisation
      • Concept applies to movement of drugs into other cellular compartmens
      • Ionisation affects not only rate at which drugs permeate membranes, but the steady-state distribution of drug molecules between aq compartments
        • Ion trapping
          • 1. Unionised drug moves across biological membrane
            • 2. Enters environment of diff pH
              • 3. Drug becomes ionised
                • 4. Ionised drug can't cross biological membrane so is trapped
    • By Carrier-Mediated transport
      • Many cells have specialised transmembrane transport systems
        • eg. for sugars, amino acids, metal ions
      • Carried out by transmembrane proteins called transporters


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