Pharmacology - Drug-receptor theories AGONIST
- 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)
- At equilibrium, law of mass action yields:
- 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
- Ka is the measure of the affinity of the drug for the receptor
- Assumption 1 - The rate of reaction is proportional to the product of the concentration of the reactants
- 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
- For each radioligand:
- 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
- 1. Need suitable radioactive ligand
- Non- Radioactive methods
- High- sensitivity detection
- Types of Agonists
- Full agonist
- Elicits max response from biological system
- Efficacy = 1
- Elicits max response from biological system
- Partial agonist
- Elicits less than max resonse from biological system
- Efficacy = 0>1
- Elicits less than max resonse from biological system
- Inverse agonist
- Produces effect opposite to full agonist
- 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
- Drug must be an agonist
- Drug receptor theory
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