drug receptor interactions 1 Flashcards
what are receptors?
what are the two roles of receptor proteins?
- receptors are specialised, localised proteins
- the two roles of recpetor proteins are to
1) recognise stimulants
2) translate this event into an activation of the cell (a cellular response)
what are interactions between drugs (agonists) and receptors like?
interactions between the drug (agonist) and receptor is loose and freely reversible and does not involve strong chemical bonds
what are 4 protein families of receptors?
- enzymes
- carrier molecules (transporters)
- ion channels
- neurotransmitters, hormones or local hormone receptors (GPCRs)
what is the lock and key analogy
- drugs (ligand) unlock the response (the chemical structure of the drug recognises the same active site) and the specificity of the lock is only relative
- the lock may be jammed (blocked by an inhibitor)
what does an agonist do and cause?
what does an antagonist do and cause?
how are there chemical similarities and differences between the two?
- agonist binds and causes a response
- antagonist binds and does not cause a response
a) they both bind to the same receptor, so there must be chemical similarities
b) one activates the receptor while the other does not so therefore there must 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”
what is Le Chatlier’s principle?
A plus B forms a complex. the more of drug A we add pushes the reaction to the right and forms more of the product (the AB complex)
what does affinity tell us?
affinity can be measured once an equilibrium complex is formed, affinity tells us how strong the binding of the drug to the receptor is.
it is a measure of binding. each drug has a different affinity to each drug due to differing specificity
what is the formal definition of affinity?
affinity is also known as the “Equilibrium dissociation constant is when the rate of associations = the rate of dissociation” (Kd)
what does the equilibrium dissociation constant (Kd) represent?
the equilibrium dissociation constant (Kd) represents the concentration of the drug required to occupy 50% of the receptors at equilibrium
Kd is:
- different for every drug
- Kd is measure of the affinity of any one drug for a receptor, how tightly bound and how easy it is to dissociate
why is the equilibrium dissociation curve (Kd) expressed in -log10 form of Kd?
what is the the pD2 of an agonist?
what is the trend between concentration of Kd and the affinity?
it is conventional to express the equilibrium dissociation curve (Kd) as -log10 of the Kd
pD2 is the -log10 of [D] that occupies 50% of the receptors at equilibrium
the lower the concentration of the Kd, the higher the affinity
what is efficacy?
when is a maximum response achieved?
- it is the maximum response of a tissue which can be obtained by occupying less than 100% of the receptors - different drugs have different capacities to initiate a response
- a maximum response is achieved when a particular stimulus is generated by receptor occupation
describe the occupancy theory
- response is proportional to the fraction of receptors occupied
- and the response = the percentage of receptors occupied
- therefore response = [DR]/[RT] = number of occupied receptors/total number of receptors
what is the trend with efficacious drugs and the number of occupied receptors?
very efficacious drugs will require to occupy fewer receptors to give a response than less efficacious ones
- spare receptors are “extra receptors” used if less than 100% of receptors are required to evoke a maximum response
- powerful drugs will produce a large stimulus upon receptor occupation, which summate until a max response is reached
