Agonists and dose response curves Flashcards
Is salbutamol
a) Alpha 2 - adrenoreceptor antagonist
b) beta 2 - adrenoreceptor agonist
c) alpha 1 - adrenoreceptor agonist
d) beta 1 - adrenoreceptor antagonist
b
B2 adrenoreceptor agonist
What is the effect of salbutamol?
Activates B2 adrenoreceptor = G2 = bronchodilation
Why are concentration response curves semi log?
Linear concentration range is too large so x axis is log
0.0001 in log form
-4
What is the dose-response relationship when looking at an isolated system?
Graded
What is the dose-response relationship when looking at the response of a popualtion?
Quantal
Describe the shape of quantal relationship on graph?
Upside down U
What 2 values and corresponding characteristics can be determined from % response and log concentration graph?
EC50 = potency Emax = Efficacy
Drug A has EC50 of 10
Drug B has EC50 of 5
Which has a higher potency?
B
Why can affinity not be calculated from % response concentration curve?
Affinity needs values for receptor occupancy - y axis would need to be % receptor occupancy
What are the 2 stages of the 2 state hypothesis?
Affinity and efficacy
How are affinity and efficacy measured?
Affinity = occupancy Efficacy = activation
Define affinity
Strength a drug binds to receptor
How is affinity calculates?
Rate of association/rate of dissociation (k1/K-1)
When a drug has a high affinity how do K1 and K-1 compare?
K1 is higher
What is Kd?
Equilibrium dissociation constant
When does Kd apply?
For any given receptor and drug in any tissue as long as the receptor is the same
Uses of Kd?
Identify unknown receptors, compare affinity fo different drugs on same receptor
Assuming there is a linear relationship between receptor occupation and effect how can Kd be calculated?
Kd = EC50
Kd has an inverse relationship with affinity
How can Kd be calculated?
K-1/K1
Rate of dissociation/rate of association
Lower Kd has what affect on affinity (and hence probably potency)?
Higher
What is potency dependent on?
Affinity
Efficacy
receptor density
Efficiency of stimulus response mechanism
EC50
The concentration of drug needed for 50% of maximum response
Relationship between EC50 and potency?
Lower EC50 = higher potency
What does it mean if a system has spare receptors?
Receptors can amplify signal so the maximum response is achieved with small receptor occupancy
Efficacy definition
Ability of agonist to activate receptor
What value on dose response curve does efficacy correspond to?
Emax
Do full or partial agonist have higher efficacy?
Full
What is full agonist?
What is partial agonist?
Max response corresponds to max response a tissue can give
Max response it elicits is lower than max response a tissue can give
Why are partial side effects used?
Alleviate side effects
What are inverse agonists?
Agonists that bind receptor and move equilibrium t left to decrease signalling pathways
They have a higher affinity for the inactive complex
What are allosteric modulators?
Ligands that bind and effect binding of endogenous agonist
Difference between positive allosteric modulator (PAM) and negative allosteric modulator (NAM)
PAM = increase affinity/efficacy of endogenous agonist NAM = decrease affinity/efficacy of endogenous agonist
Tachyphylaxis?
Desensitisation of receptor due to continued/repeated use
What causes desensitisation?
Conformational change, internalisation of receptor, altered drug metabolism
After tachyphylaxis, if the drug is stopped and started again at another date how does sensitivity change?
Increased
