introduction to drug action Flashcards
What causes receptor occupancy
when a ligand binds to a receptor without causing a tissue response
why do drugs need specificity
must act selectively for a specific receptor, otherwise could bind to non-target receptors and cause a response
When are there equilibrium when forming the ligand-associated complex
concentration of ligand required to make 50% of the receptors bound, 50% free
what is the association (forward) rate constant
k + 1
what is the disassociation (backward) rate constant
k-1
What type of bonds allow ligands to easy bond/disassociate with receptors
ionic
LdF’s
how is a drug determined to have high affinity for a receptor
low concentration required to reach equilibrium between association and disassociation
How is the disassociation constant formed
KA = k-1 / k+1
What is the disassociation constant used for
to compare drugs affinities for receptors
ensures target receptor only
Which equation models the relationship between ligand concentration and receptor occupancy
Hill-Langmuir equation
What is KA
the concentration of ligand required to occupy 50% of the receptors
How is the KA found using a graph
increase the ligand concentration until fractional occupancy reaches 50%
What does a lower KA mean
higher affinity of ligand for receptor
what are the 2 ways to compare drug affinity
disassociation constant
radioligand displacement (Ki)
what is efficacy
the tendency for an agonist to activate the receptor
why can a ligand with affinity for a receptor not activate a tissue response
ligand may bind but be metabolised before causing an effect
Why do some agonists only need to occupy a small % of receptors to give a maximal response
signal amplification
what is drug potency
the concentration/amount needed to reach EC50
what does drug potency depend on
receptor affinity/efficacy
tissue parameters
How do partial agonists work
an agonist that will not activate a full tissue response even with 100% receptor occupancy
What is the function of a reversible competitive antagonist
competes for binding site
disassociates
How can the affects of reversible competitive antagonism be overcome
if agonist concentration is increased
what happens to an agonist concentration response curve in the presence of an antagonist
shifts right - higher agonist concentration required for max effect
