Receptors 3

Affinity

How well the drug interacts with the receptor

can be measured using a binding assay. this is a direct measure of the physical interaction between a drug and a receptor

Specificity

how selective is drug binding to one type of receptors but not to other types of receptors

Efficacy

this tells us how effective a drug is at producing a particular receptor response

potency

this tells how much of the drug is required to produce an effect

Analyze radioligand binding data

a drug may bind to many biological targets

high affinity - specific binding

low affinity - nonspecific binding

subtract non-specific binding from total binding to measure the amount of specific binding

radioligand binding data - total binding

radioligand binding data - non specific binding

radioligand binding data - specific binding

receptor fractional occupancy

used in receptor-drug binding curves

= [Receptor bound with drug] / [(free receptor) + (receptor bound with drug)]

K_d - equations

equilibrium dissociation constant

= tendency of RD complex to dissociate / tendency of R&D to form RD complex

= [R] [D] / [RD]

Affinity = 1/K_d

K_d - definition

drug concentration when 50% of receptors are bound with the drug

Functional assay

a measure of the changes in the function of the receptor

used for evaluating potency and efficacy

EC₅₀

the concentration of a drug that produces 50% of maximal response

measure of potency

higher potency = lower value

efficacy - graph evaluation

reflects the upper limit (maximal response) achieved by a drug on the dose-response curve

potency - graph evaluation

inversely correlated to EC₅₀

Factors affecting a drug’s clinical effectiveness

potency

efficacy

ability to reach receptors (route of admin, absorption, distribution, clearance)

Agonist

binds to a receptor and activates it

shifts equilibrium towards active state

Antagonist

binds to a receptor but does not activate signaling

does not change equilibrium between active/inactive but can prevent agonist binding

inverse agonist

produces a response opposite that induced by a full agonist

shifts equilibrium towards inactive state

Partial agonist

produces a lower response than do full agonists

Chantix (Varenicline)

nicotinic AChR partial agonist

used as replacement therapy in smoking cessation

instead of nicotine - full agonist

Narcan (naloxone)

pure opioid receptor antagonist

no/little symptoms by itself

for Tx opioid OD induced respiratory depression, CNS depression

IM injection or nasal spray (effective after 2-5min)

competitive antagonists

compete for same binding site as agonist

shifts curve to the right

sufficiently high concentrations of agonists can overcome a given concentration of competitive antagonists

max response not changes, change in EC₅₀

noncompetitive antagonist

bind to allosteric site on receptor and interferes with agonist binding or modifies receptor activity

can NOT be overcome by high concentrations of agonist

max response reduced (curve shorter)

EC₅₀ may or may not change