Drug-Receptor Interactions 1 Flashcards
Describe receptor theory
Interaction between the drug and receptor is loose and freely reversible and does not involve strong chemical bonds.
What are receptors in receptor theory?
Receptors are specialised, localised proteins whose role it is to recognise stimulants and translate this event into
an activation of the cell.
What are the four regulatory protein families that are are commonly drug targets and are covered by the term receptor?
- Enzymes
- Carrier molecules (transporters)
- Ion channels
- Neurotransmitter, hormone or local hormone receptors
What is the lock and key analogy of receptor theory?
Drugs unlock the response
The specificity of the lock is only relative The lock may be jammed
(Lock is receptor, drug is key)
What are the similarities and differences between agonists and antagonists that work on the same receptor?
a) Both bind same receptor, so must be chemical similarities
b) One activates the receptor, other does not: Must also be chemical differences
What is the law of mass action?
“The rate of a chemical reaction is proportional to the product of the concentration of the reactants”
[A] + [B] [AB] Where
–> = K1
What is the resulting equation when the Law of Mass Action is applied to pharmacology?
[D] + [R] [DR] Where
–> = K1
What is equilibrium in the Law of Mass Action applied to pharmacology?
Equilibrium when rate of associations = rate of dissociations
What is the equilibrium dissociation constant?
The equilibrium dissociation constant (KD) represents the concentration of drug required to occupy 50% of the receptors at equilibrium.
The KD is:
- different for every drug
- a measure of the affinity of any one drug for a receptor
What is affinity in the Law of Mass Action applied to pharmacology?
It is conventional to express the equilibrium dissociation constant (KD) as -log10 of the KD. This is called the pD2 for an agonist:
pD2 = -log10(KD)
pD2 is the -log10 of [D] that occupies 50% of the
receptors at equilibrium
pD2 is affinity!*
What is efficacy in the Law of Mass Action applied to pharmacology?
The maximum response of a tissue can be obtained by occupying less than 100% of the receptors
Who discovered the nature of drug efficacy and what did they discover?
Robert Stephenson (1956)
Different drugs have different capacities to initiate a response
A maximum response is achieved when a particular stimulus is generated by receptor occupation
How are biological responses to drugs classified and what relationship is associated with this?
Biological responses to drugs are graded
These responses and their comparative sizes
can be measured
There is a systematic relationship between the drug concentration and the magnitude of the response obtained
What is occupancy theory?
Response α fraction of receptors occupied I V Response = % of receptors occupied I V Response = [DR]/[RT]
Where
[DR] = number of occupied receptors
[RT] = total number of receptors
What is the relationship between occupancy theory and the Law of Mass Action applied to pharmacology?
[D] + [R] [DR] (inactive) [DR]* (active)
Where first is broken down into:
= K2
Where second is broken down into:
= β
Where first [DR] is the occupancy stage
And second [DR] is the activation stage
D is drug
R is receptor
DR is occupied receptor
K1 is the rate constant of associations
K2 is the rate constant of dissociations
α is the rate constant of receptor inactivation
β is the rate constant of receptor activation
