Drug Receptor Interactions Flashcards
Describe drug receptor interactions
A specific protein that recognizes a ligand leading to the formation of a ligand receptor complex that initiates a series of biochemical consequences leading to a biological response
There are usually endogenous ligands for every receptor
What’s an orphan receptor?
When we don’t know the endogenous ligand for a receptor is called an orphan receptor
What makes a receptor a receptor?
Binding is specific, sometimes sterospecific (there is an endogenous compound a neurotransmitter, hormone, etc. that binds to the receptor in a specific way; compounds with similar structure will often bind to the same receptor)
There is a finite binding capacity for receptors (there is a limited number of receptors and binding can be saturated, i.e., all receptors may be occupied)
There is a cause an effect relationship between ligand binding and biological response
Affinity of binding is high
Receptors are tissue specific (i.e., they are in the tissues that need to respond to the ligand)
Ultimately the ligand acts as a chemical signal that produces the biological response at a specific tissue
What forces do drugs use to bind receptors?
Dispersion forces (for protein interactions dispersion forces are referred to as hydrophobic interactions)
Hydrogen bonding
Ionic
Ion dipole
How can we determine a relationship between the binding of a receptor and the biological response?
We can assume that there is some relationship between the number of drug-receptor complexes and the magnitude of biological response
What is the receptor occupancy theory?
If we make the assumption that the magnitude of the biological response is directly proportional to the amount of receptors that are bound with drug, we can show that the effect of a drug is related to the fraction of bound receptors. Assumptions: maximum biological effect is only reach when all receptors are bound; this process follows the laws of mass action
What is Kd?
The equilibrium dissociation constant . It is unique for each receptor and ligand. It is a measure of how the equilibrium is displaced to free D or free R
What does a small Kd represent?
A small Kd means there is more DR and therefore more biological response, which indicates tight binding. Many drugs have binding sites between 1x10^-9 to 1x10^-6 M
What is Ka?
1/Kd. It is the the affinity constant. It’s units are L/mol. It is somewhat more intuitive in that the higher the affinity constant, the tighter the binding
What is the advantage of Kd?
If the receptor has a Kd of 1 uM, we know that a 1 uM [drug] will produce half maximal receptor binding
What is intrinsic activity?
According to the receptor occupancy theory, the effect is proportional to the amount of receptor complexes. The instrinic activity (alpha) or efficacy is a constant of proportionality which measures the ability of the drug to produce an effect by forming a drug receptor complex. Alpha is independent of Kd
What is ED50?
ED50 is the dose needed to achieve half maximal response. The ED50 of a drug is its potency; the lower the ED50, the less drug needed to get the maximal response
What more important: potency or effect?
Potency is not as important as clinical effect. A drug could have a high potency but a small effect, whereas a low potency drug could have a great effect
If Kd and ED50 are different, why do they have the same values?
They have the same values in receptor occupancy theory because we defined the effect as being directly proportional to receptor binding and defined maximum effect as being achieved when all receptors are bound
What is an agonist?
Agonists bind to receptors and have affinity for the receptor and have intrinsic activity efficacy
Most receptors have endogenous agonists
Drugs that bind to the receptor and have intrinsic activity are agonist
Drugs that bind to the receptor and have intrinsic activity are agonists
