Pharmacology - Drug-receptor theories AGONIST

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  • Created by: Sophie
  • Created on: 14-01-13 12:34
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  • Drug-receptor theories- AGONIST
    • Drug receptor theory
      • Drugs acting on receptors may be agonist or antagonist
      • Agonists initiate changes in cell function, producing effects of various types
      • Agonist- elicits a response from biological system by interacting with receptor
      • Assumption 1 - drug (D) binds reversibly to receptor (R) to form drug-receptor complex (DR)
        • D + R <=> DR
      • Assumption 2 - Biological response is elicited only when D is bound to R
    • Law of Mass Action
      • Assumption 1 - The rate of reaction is proportional to the product of the concentration of the reactants
        • At equilibrium, law of mass action yields:
          • Assumption 1 - [DR] = (Rmax x D) / (Ka + D)
      • Equilibrium constant - Ka
        • Ka is the measure of the affinity of the drug for the receptor
          • High affinity = low value Ka
        • To estimate Ka the value of Ka is [drug] when 50% of receptors are occupied by drug
    • Radio-ligand binding
      • radioactive ligand = radioligand
      • 5 steps:
        • 1. Select radioligand - high specific activity, high affinity
        • 2. Source of receptor - usually membrane preparation (cells, tissues)
        • 3. Incubate receptor with radioligand until reaches equilibrium
          • vary radioligand for each measure of 1) total binding 2) nonspecific binding
        • 4. Collect receptors
          • Separate radioligand bound to receptor from unbound radioligand
        • 5. Measure amount of raioligand bound to receptor
      • Analysis of assays
        • For each radioligand:
          • Determine total and non-specific binding
          • Calculate specific binding
      • Problems
        • 1. Need suitable radioactive ligand
          • Custom syntheses are too expensive
        • 2. Depletion of radioactive ligand
          • High affinity ligands are used at low concs.
        • 3. Drug binding not explicitly linked to a biological effect
          • 4. Hazards of radioactive materials and waste disposal
    • Non- Radioactive methods
      • High- sensitivity detection
    • Types of Agonists
      • Full agonist
        • Elicits max response from biological system
          • Efficacy = 1
      • Partial agonist
        • Elicits less than max resonse from biological system
          • Efficacy = 0>1
      • Inverse agonist
        • Produces effect opposite to full agonist
    • Problems with use of bioassay to determine Ka
      • Drug must be an agonist
        • Theres a more complex analysis for antagonists
      • If drug is metabolised then Ka will be overestimated
        • Drug at receptor will be more than drug added
      • Spare receptors
        • Error in assumption that 100% receptor occupancy is sneeded for max response

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