Pharmacodynamics Flashcards
What is pharmacodynamics?
What the drug does to the body
What is a ligand?
Molecule that binds specifically to a receptor
What is an agonist?
Molecule that activates a receptor
What is an antagonist?
Molecule that blocks the binding of an endogenous agonist
What is affinity?
Measure of ability to bind to a receptor
What is intrinsic efficacy?
Measure of receptor activation
What is efficacy?
Ability of a ligand to cause a measurable response
What is used to determine drug action?
Concentration of drug molecules around receptors (in molarity)
What are the features of agonists?
Have intrinsic efficacy
Have efficacy
Have affinity
What are the features of antagonists?
Have affinity
No intrinsic efficacy
What is Kd?
Dissociation constant
Measure of affinity
What does a low Kd mean?
High affinity
What does a high Kd mean?
Low affinity
What is Bmax?
Maximum biding capacity
How is Kd calculated?
Drug concentration at 50% occupancy of receptors
What are the usual responses of ligand binding?
Change in signalling pathway
Change in cell/tissue behaviour
What is EC50?
Effective concentration giving 50% of maximal response
What does EC50 measure?
Agonist potency
What does EC50 depend on?
Affinity
Intrinsic efficacy
What are spare receptors?
Receptors that exist when a lower % binding can cause a 100% response
Why do spare receptors exist?
Amplification in the signal transduction pathway
Response limited by post-receptor event
Why do we need spare receptors?
Increase sensitivity
Changing receptor number changes agonist potency
What happens to receptor numbers with low activity?
Up-regulation
What happens to receptor numbers with high activity?
Down-regulation
What is the relationship between Kd and EC50 with a full agonist?
EC50 = Kd
What is the relationship between Kd and EC50 with a partial agonist?
EC50 ~ Kd
What are the uses of partial agonists?
Can allow a more controlled response
Work in the absence/low levels of ligand
Can act as antagonist if high levels
What are the main types of antagonist?
Reversible competitive antagonism
Irreversible competitive antagonism
Non-competitive antagonism
How does a reversible competitive antagonist work?
Blocks ligand from binding with receptor
Greater [antagonist] = greater inhibition
How can a reversible competitive antagonist be stopped?
Increase concentration of agonist
How does an irreversible competitive antagonist work?
Binds with receptor and dissociates slowly or not at all
How do non-competitive antagonists work?
Bind to orthosteric site and change shape of receptor so ligand cannot bind
