Receptor theory Flashcards
What is receptor theory?
That most drugs act by binding to receptors
Does RT explain all drug actions?
No, chemical action or other properties
Example: Antacids - alkaline ions that chemically neutralize gastric acid in the stomach
Drug definintion
A chemical compound that is administered to produce a desirable physiological or psychological effect
What is a side effect?
Undesirable changes caused by a drug
What is a receptor?
A molecule a drug can bind to which will cause a physiological change
How does a drug bind its receptor?
Weakly and reverisibly
Weak binding is
van der Waals force, H-bonds, ionic interactions
Reversibly binding is
Enzyme-substrate binding
Four main types of receptors
ion channels, G-protein coupled receptors, enzymatic, intracellular
What is the equation for receptor theory?
D + R > [DR] > effect
What are the properties of receptors?
Recognition and transduction
Explain what the conformation of the receptors must allow
Must allow saturability, reversibility, stereoselectivity, agonist specificity and tissue specificity
What is the transduction in receptors?
The spreading of the signal which leads to a physiological output
What is an agonist?
A drug that binds to a receptor eliciting a cellular response
What is an antagonist?
Prevents the action of an agonist
What makes a drug an agonist?
Must have an affinity for the receptor and it must have an effect
What are natural agonists?
Naturally occurring molecules that cause an effect, an example would be endorphins
What is dose response?
The systemic relationship between the drug concentration and the magnitude of the response obtained
Law of mass action
The rate of a chemical reaction is proportional to the product of the concentration of the reactants
Do all receptors need to be occupied to give the max effect?
No
what is the rate that the drug receptor complex disassembles?
Kd = K1/K2 = [D][R]/[DR
What is the rate that the drug receptor complex assembles?
Ka = 1/Kd = K2/1=[DR]/[D][R]
Limitations of the law of mass action
- assume that all receptors and ligands are equally available to each other
- Binding of drug and receptor is reversible
- The binding of drug and receptor leaves them unaltered
- There are no ambiguous partial states
Occupancy theory
The effect is proportional to the number of receptors that are occupied
Occupancy theory equation
Response = number of occupied receptors/ total number of receptors
What does logging the x axis actually do on a dose response curve?
Helps you understand whats happening at the different concentrations
What is the S shaped log dose curve called?
Sigmoid curve
What way will the log dose curve shift if it is a less potent agonist?
Right
What will a partial agonist do to the log dose response curve?
move it down
What will positive cooperativity do to the curve?
steepen it
What will negative cooperativity do to the log dose curve?
flatten the curve
What are the 4 key parameters of the dose response curve?
- base line
- slope
- EC50
- maximal response
What is a competitive antagonist?
a drug which interacts reversibly with the receptors
A non competitive antagonist
a drug that binds with the receptors irreversibly
What is a pA2 value?
An estimate of the concentration of agonist that is needed to double the concentration of agonist necessary to elicit the original response
How does a competitive antagonist shift the curve?
to the right
How does a non-competitive antagonist shift the curve?
moves it down
What are the 2 properties of drugs?
Affinity and efficacy
What is affinity?
a measure of the concentration range over which a drug binds to its receptor
what is efficacy?
The ability of the drug to generate/ intiate a response once bound to the receptor
what is the efficacy of an antagonist?
0
How do you end the response?
receptors can be
- desensitized
- Internalised
- downregulated
