Use LEFT and RIGHT arrow keys to navigate between flashcards;
Use UP and DOWN arrow keys to flip the card;
H to show hint;
A reads text to speech;
51 Cards in this Set
- Front
- Back
|
What are ligands? |
Drugs which bind to receptors |
|
|
What do agonists do? |
Bind to and activate receptors |
|
|
Agonists have ____ and evoke _____. |
Efficacy; responses |
|
|
What do antagonists do? |
Bind to and do not activate receptors |
|
|
Agonists have ____ and _____ the action of agonists. |
Zero efficacy; block |
|
|
What is affinity? |
A measure of how well a ligand binds to a receptor |
|
|
What is efficacy? |
The ability of a drug to activate a receptor and cause a response |
|
|
What is selectivity/specificity? |
The ability of a ligand to bind to a specific binding site or of a receptor to only bind certain types of molecules |
|
|
What is potency? |
The amount of drug required to evoke a given response |
|
|
A ligand with a higher ____ is more ____ for a receptor. |
Affinity; specific |
|
|
What controls drug binding levels? |
Speed of diffusion, bonds between the ligand and receptor, speed of 'unbinding' (length of time bound to receptor) |
|
|
What determines the speed of drugs reaching a receptor? |
The rate of ligand diffusion |
|
|
What types of bonds determine how a ligand fits into a receptor? |
Electrostatic, hydrophobic, and hydrogen bonds |
|
|
What does it mean that binding is a dynamic equilibrium? |
Drugs will not bind permanently to receptors-- binding and unbinding happens in a balance |
|
|
What factors affect the selectivity of binding? |
Mostly the shape and compatibility of the ligand and receptor-- also electrostatic and hydrophobic forces |
|
|
How is drug binding measured? |
Separating the amount of free ligand from bound ligand to determine how much ligand has bound |
|
|
What is needed to measure drug binding? |
A detectable ligand (usually an antagonist with a tag) and a source of receptors |
|
|
What is the equilibrium equation for drug binding? |
R + L* ⇌ RL* |
|
|
What is L*? |
The amount of free ligand |
|
|
What is R? |
The amount of receptors |
|
|
What is RL*? |
The amount of receptor-bound ligand |
|
|
How is a specific binding assay conducted? |
Saturation with an unlabelled drug to determine non-specific binding, which is then subtracted from the total binding
|
|
|
What is the Bmax of a specific binding plot? |
The number of binding sites present |
|
|
What is the Kd of a specific binding plot? |
The affinity-- the concentration of ligand which binds to half the receptors |
|
|
What is the shape of a specific binding plot? |
A hyperbolic curve |
|
|
What is a Scatchard Plot? |
A graph which plots bound vs. free |
|
|
What is the benefit of using a logarithmic concentration scale for specific binding plots? |
They have more detail and make it easier to determine KD |
|
|
What does a Scatchard Plot look like? |
A straight line with a negative slope |
|
|
What does the slope of a Scatchard plot equate to? |
-1/KD |
|
|
What does the x-axis of a Scatchard plot equate to? |
The Bmax |
|
|
What are the axises of a Scatchard Plot? |
Bound ligand vs. Bound:Free ratio
|
|
|
What is KD? |
The equilibrium dissociation constant |
|
|
How is KD determined (not graphically)? |
The forward rate of ligand-receptor association vs. the reverse rate of dissociation |
|
|
2 drugs both bind at the histamine H1 receptor, Drug X has a dissociation constant (KD) of 1x10-9 M, Drug Y has a KD of 3x10-9 M. Which one has the higher affinity? |
Drug X-- lower KD means lower amount required for the same effect |
|
|
Which of theses drugs has the highest affinity at a receptor? Drug A with a log KD of -5 Drug B with a log KD of -6 |
Drug B-- lower KD means lower amount required for the same effect |
|
|
How are competitive ligand binding essays performed? |
Using fixed concentrations of receptors and ligands, with increasing concentrations of competing ligand X to determine X's ability to displace binding |
|
|
What is Ki? |
The affinity of the competing ligand, i.e. its ability to displace ligand binding |
|
|
Ki inversely relates to what? |
Affinity-- lower Ki means lower amounts needed to compete the same amount |
|
|
What does Ki measure? |
The concentration of the competing ligand required to displace 50% of the original ligand |
|
|
How does Ki differ from Kd? |
Ki is an estimate of affinity-- assay conditions will affect Ki values (e.g. the concentration of the radioligand and the type used) |
|
|
How do binding studies indicate selectivity? |
Screening a drug against many different receptors indicates whether the drug binds selectively or not |
|
|
Do binding studies indicate the function of a drug (agonist/antagonist)? |
No |
|
|
What makes a drug selective? |
Its ability to activate the receptor (potency and efficacy), where it binds to the receptor, tissue selectivity |
|
|
What is tissue selectivity? |
Whether a drug is able to access the receptor |
|
|
What is the difference between affinity and selectivity? |
A drug is only selective if it has a high affinity for that receptor but NOT any others |
|
|
What is the occupational model of agonism? |
The idea that an agonist binding to a receptor produces both a conformational change and an effect in the cell |
|
|
How does the occupational model of agonism measure agonist actions? |
The more receptors occupied the greater the effect-- direct relationship |
|
|
What is the major failing of the occupational model of agonism? |
Too simplistic-- in practice the relationship between occupancy and response is not linear, does not account for some complex properties of drugs |
|
|
What is the Emax of a concentration response curve? |
The maximum possible response which a drug has on a cell or tissue |
|
|
What is the EC50? |
The concentration of a drug which causes half the maximum effect of that drug |
|
|
What is the EC50 a measure of? |
The potency of an agonist (not affinity or efficacy) |
