Agonists And Dose Response Curves Flashcards
What do agonists and receptors form and give example
Agonist receptor complexes
Salbutamol and B2
Form camp
Bronchodilation
Why is dosage important in pharmacodynamics
Need a certain dose for an effect but also there’s a line between toxicity
What is plotted on a dose response curve
Agonist concentration/ dosage
Against response % of the body
What is a GRADED dose response curve
Response of a particular system (person or tissue) to an AGONIST CONC
What is a QUANTAL dose response relationship curve
Where the response of the population/all tissues included
Plotted against the dosage of AGONIST OR ANTAGONIST CONC
Why is the graph placed on log scale
To fit the maximum dosage response relationship
Much higher dose needed
What is the maximum response called regardless of dosage
Efficacy / eMAX
What does EC50 mean on a dose response curve
The concentration/dose needed to produce a 50% response
What does the lowest point on graph show
The threshold dose needed for response
Explain the 2 state hypothesis
First state is
Drug + receptor —-> complex
The forward binding to this is K1
Reverse (dissociation of drug to receptor) = K-1
Next state is
AR complex —-> activated
Reverse is inactivion of complex
What does the first state (forming complex) show
The occupancy and affinity of the drug and receptor
What does the second stage (activation) show and presume
Shows efficacy of the drug to form response
Suggests it’s either in the inactive stage or the active (only 2)
How would you measure specific drug binding to receptors
You would measure the max number of drug bound (saturation) - non specific drug binding
What is the max drug binding number called
to determine number of drugs bound - non specific drugs
Bmax
What is kD a measure of
Affinity
It is the equilibrium dissociation constant
How is the kD measured and what does it tell us (equilibrium dissociation constant)
K1 association / k-1 dissociation
The lower the kD = higher affinity
When can kD affinity be equal to EC50
It is the same as the EC50 ONLY when response is proportional to occupancy of receptors
Why can kD be used to identify drugs or receptors
Because the kD of a drug receptor complex is the same in any tissue and person
What is EC50 a better measure of than kD because response isn’t proportional to occupancy
Potency
What is potency and why is it the same measure as EC50
Potency is the dosage/ conc needed to produce an effect
If a drug has a high potency (low EC50) it means they produce a response even at a lower concentration
What is potency dependant on
Affinity of the drug
Efficacy of the drug (ability to activate)
Receptor density
What are spare receptors
The fact that the proportion between occupancy and response isn’t linear
Some receptors can produce a higher response even in lower numbers
Spare receptors are ones not needed
What is efficacy
Ability of an agonist to evoke a response in receptor
Maximum is regardless of the dose given
EMAX = max efficacy
What is a full agonist
An agonist with high efficacy
They have an incline to the active state despite concentration
What is a partial agonist
Agonist with lower efficacy showing low response
The equilibrium can’t move into the active state as well even if all receptors occupied
What are partial agonists used for and give example
They are a therapy drug which are used to stop full stimulation and addiction by have lower response
Eg tamoxifen which binds to oestrogen receptor as a partial agonist to stop breast cancer
What is the drug called which helps smoking addiction via partial agonist
VARENICLINE - binds to nicotine receptors with lower stimulation as nicotine
What did lape et al 2008 find
Some receptors can be respond the same to partial and full agonists
Eg glycine and nicotinic ach
They are in a flip state between active and inactive
What is the model called that suggested receptors have 4 active states instead of 1
Ternary complex model
What did the ternary complex model show
Receptors can become active without an agonist present and also can become gcpr and active that way
What is it called when a receptor becomes active on its own
Constitutive activity
What are inverse agonists
Agonists which have higher affinity for the inactive state of complex (low efficacy)
They turn receptor off
Give example of inverse agonist which many antagonists are
H2 receptor and cimetidine
What did kenakin find about inverse agonists
85% of competitive antagonists were actually inverse agonists
What are allosteric modulators
Drugs which bind to a seperate binding site and increase efficacy / response of the receptor by increasing affinity for agonist
How is benzodiazepine an allosteric modulstor
It binds onto gaba ion channel and increases affinity for gaba
This increases efficacy
Response is more Cl floods in
Calms anxiety
What 2 types of allosteric modulators are there
Negative - decrease affinity and efficacy
Positive -
Why does deug efficacy decrease with repeat administration
receptor desensitised
What is another word for drug response diminishing (efficacy)
Tachyphylaxis
What are major players in tachyphylaxis
Gradual change in receptor shape
Receptor internalisation (sequestration)
What other things can affect drug efficacy over time
Drug metabolism
What is the therapeutic index?
The window/dosage of the antagonist which has desired effects and isn’t an overdose
Why is it good to have a large TI
Because it makes it easier to dose it and not overdose eg penecillin has large therapeutic index
