PBL 2 PHARMACOLOGY - agonsits and antagonists Flashcards
what is an agonist?
an activating molecule
what is an antagonist?
an inhibiting molecule
what is efficacy?
the tendancy of a drug to activate a receptor
what is the name for a drug with maximum efficacy?
full agonist
what is the name for a drug with zero efficacy?
antagonist
how do antagonists work?
- when they bind they don’t activate the receptor
- they exert their effects by blocking activity of an agonist
what happens if no agonist is present?
there is no measurable effect — a functional assay relies on receptor activation to produce a measurable effect
what does the functional Gaddum equation describe?
the effect produced by agonist D, in the presence of a competitive antagonist I
what is meant by Ki?
the antagonist dissociation constant — the antagonist affinity
does binding affinity relate to efficacy?
binding affinity, as measured by Kd, does NOT relate to efficacy
what is potency of a drug a measure of?
a measure of the concentration at which the drug can evoke a specified effect
competitive antagonist are surmountable. what does this mean?
the antagonism can be overcome by increasing the agonist concentration
is there a change in maximum response for an agonist if a competitive antagonist is present?
no
what is competitive antagonism characterised by (in terms of concentration response curve and EC50) ?
characterised by a parallel shift to the right of the concentration curve with an increase in EC50
what is EC50?
the conc of agonist giving 50% of the max effect
what are Kd and Ki?
a measure of drug affinity
what is the difference between Ki and Kd?
- essentially the same thing = a measure of drug affinity
- Kd is normally used when the data have come from a saturation assay and the affinity has been measured DIRECTLY
- Ki is used when the measurement of affinity has been made INDIRECTLY (eg. competition binding assay or via calculations from the Gaddum equation)
what is pKi? pKi vs Ki?
- a measure of affinity
- Ki values are not normally distributed but pKi values are — we can take the negative log of Ki to generate pKi
what is pA2?
- the negative log of the concentration of antagonist required to double the EC50 for the agonist
- measure of potency (as we are defining a “specific effect”)
what is pA2 obtained from?
the concentration of antagonist that gives a concentration ratio of 2
CR = 1 + ( [I] / Ki )
what is pA2 effectively equivalent to?
pKi
what is tone?
the underlying level of activation of a tissue
what is a partial agonist?
a drug that cannot fully activate a receptor, even when all the receptors in the system are occupied
compare the EC50 values of a full agonist and partial agonist
they are the same
list the 4 parameters of competitive antagonist affinity. which one isn’t included and why?
- Kd
- Ki
- pKd
- pKi
(not pA2, this is a measure of potency, because it is a “concentration to produce a defined effect”)
what is affinity?
the tightness of binding of a ligand
what is efficacy?
the degree to which a ligand can activate a receptor (max effect a ligand can produce)
what is acetylcholine?
a full agonist
when does a receptor show spontaneous activity?
in the absence of an agonist
what are adrenaline and noradrenaline?
full agonists
according to the 2 state model, what does a full agonist have a much higher affinity for?
the active state
why is the underlying level of spontaneous activity not affected by antagonists?
because these drugs do not select between the inactive and active states of the receptor — bind to both equally with equal affinity
what type of ligand reduces spontaneous activity?
partial agonists — bind tighter to active state but doesn’t select between the 2 states as much as a full agonist
what state to inverse agonists bind tighter to and what is the effect of this?
bind tighter to the inactive state — reduce spontaneous activity
how do inverse agonists differ from competitive antagonists?
inverse agonists will reduce spontaneous activation of the receptor
