wk 1 General principles and drug targets Flashcards
What is affinity
the ability of a drug to bind to the receptor (or another drug target)
(affected by the number of bonds/ attractive forces between drug and receptor)
What is efficacy?
The ability of a drug: receptor complex to elicit a biological response
What is specificity?
The ability of a drug to bind to one receptor without affecting another
What is potency?
the biological response in relation to the amount administered
What is the equation related to affinity?
A+R <—> AR
(forward reaction= k +1 and backward reaction= k-1)
KD= [A][R] \ [AR]
State the law of mass action?
” The rate of a chemical reaction is proportional to the product of the concentration of the reaction”
A + R <—-> AR
k+1 and k-1 are rate constants for the forward and backward reactions:
Rate of forward reaction = k+1 [A] [R]
Rate of backward reaction = k-1 [AR]
Describe the dissociation constant at equilibrium.
KD=[A][R]/[AR]
In the form of a Michaelis-Menten equation
[AR]/RT=1/ A=KD/[A]
Where RT is the total number of free [R] and bound [RA] receptors
[AR]\RT IS PROPORTIONAL TO KD
Draw and describe the dose-occupancy curve?
At equilibrium, what is KD?
KD is the concentration of ligand required to occupy half of the number of available receptors
i.e. when [A] =[KD],[RA]=0.5RT
The lower the KD, the higher affinity for the receptor
What is KD?
Dissociation Constant (conc. drug required to occupy 50% sites at equilibrium)
What is Bmax?
Total number of binding sites in the prep
Draw and describe the log dose-occupancy curve?
What does the competition binding experiment determine?
IC50, the concentration of ligand causing 50% inhibition of radioligand binding
What is the equation related to specificity?
KD1=[A][R]/[AR]
KD2=[A][R]/[AR]
How is efficacy measured?
Efficacy is measured by monitoring the biological response of a drug at increasing concentrations
Describe what the receptor actions are; agonist and antagonist?
Agonist- Transduction mechanism: ion channel opening , enzyme activation/inhibition, ion channel modulation, DNA transcription
(increases or decreases biological response and used the second messenger)
ANTAGONIST- no intrinsic effect: but endogenous mediators blocked.
( doesn’t have to be competitive binding)
What is the endogenous ligand and antagonist efficacy?
endogenous ligand has a relative efficacy of 1.0 and an antagonist has an efficacy of 0
Does the total amount of receptors have an effect on total amount of response?
yes
Draw a receptor action of response against [drug] curve?
