Receptor Theory Flashcards
Define efficacy
The likelihood of activation of a receptor and stimulation of cellular response.
This is dependent on intrinsic efficacy and cell dependent factors.
Since intrinsic efficacy
The ability of a ligand to activate a receptor
What is Kd? Measure of?
Kd is the dissociation constant.
Concentration of ligand at which half of all of the available receptors are bound.
Measure of affinity.
Lower Kd = greater affinity
What is EC50?
The effective concentration of drug required to give 50% of the maximum response.
It is a measure of potency.
Lower EC50 = greater potency
Define potency.
A measure of the amount drug required to produce an effect of give magnitude.
What is Athsma
Reversible airflow obstruction caused by bronchoconstriction
What are two drugs used to treat asthma
Salbutamol salmeterol
Beta2 agonists
How does salbutamol target beta 2
Kd low for beta 2, high for beta1
Route of administration - oral spray
Beta 2 selective efficacy
How does salmeterol target beta2
Much higher affinity for beta 2 than 1
What do spare receptors result in? EC50 and Kd
Less that 100% receptor occupancy results in 100% response
EC50
What is the relationship between receptor occupancy and response
Transduction system and amplification by second messenger
The level if endogenous agonist
Number of receptors
Properties of the tissue
What is the consequence of having more receptors than requires
Increased sensitivity, allowing for response at low agonist concentration.
How does number of spare receptors affect potency?
Increasing number of receptors increases potency.
EC50 gets
How does the plot of dose response look for a partial agonist.
Plateaus at a lower Emax than full agonist
May have higher potency.
Describe a clinical use for a partial agonist.
Opiod receptor partial agonists allow adequate pain control with less respiratory depression and allow withdrawal from full agonist morphine.
Give 3 types of antagonist
Reversible competitive
Irreversible competitive
Non competitive
How does the presence of an reversible competitive antagonist shit the dose response cure?
Shift to the right.
Still reaches Emax eventually
Describe how irreversible competitive antagonist shifts the dose response curve.
Shifts to the right
Can reach Emax at low antagonist concentration
Reaches a lower Emax at higher antagonist concentrations as spare receptors are filled.
Describe the changes in the presence of a non competitive antagonist.
Binds to allosteric site.
Shifts dose response curve to the right.
Lowers Emax
Similar to irreversible, differentiated by tests
Describe except or desensitisation
Repeated stimulation may lead to changes in responsiveness.
Prevent damage from excess stimulation
May occur in response to phosphorylation
May occur in response to reversible internalisation.
Describe homologous desensitisation
Repeated stimulation of single receptor population reduced the response from that receptor population
Describe heterologous desensitisation
Occurs when a single receptor has been continuously stimulated resulting in responses from other agonists becoming blunted.
Define affinity
The degree to which a ligand binds to its receptor
