Flashcards in Membranes and receptors - 8 Deck (28):
Define a ligand
A molecule (or e.g. ion) that binds specifically to a receptor.
Is a ligand's ability to bind to its receptor. The higher a ligand's affinity for its receptor the stronger the binding in the receptor-ligand complex.
The ability of a ligand to cause a (measurable) response. This is goverened by intrinsic efficacy PLUS cell/tissue-dependent factors.
A ligand that binds to a receptor and activates it.
Define partial agonist
Define intrinsic efficacy
How good an agonist is at generating the active state of a receptor.
A ligand that binds to a receptor and stops it from being activated by its agonist.
Define functional antagonism
Define reversible competitive antagonism
Define non-competitive antagonism
How do drugs exert effects?
Binding to targets - these are mainly proteins, with the exception being some antimicrobial drugs and anti-tumour drugs which bind DNA.
What percentage of the drugs on the market target GPCRs?
~30% (~50 targets)
What is a biologic?
any pharmaceutical drug product manufactured in, extracted from, or semisynthesized from biological sources. Different from chemically synthesized pharmaceuticals, they include vaccines, blood, or blood components, allergenics, somatic cells, gene therapies, tissues, recombinant therapeutic protein, and living cells used in cell therapy
What factor is critical in determining a drugs action?
The concentration of drug molecules around their receptor target.
What is the molar range that is optimal for drugs to work at?
What does 1 mole of a substance mean?
It is Avagadro's constant: 6 x 10^23 molecules of that substance.
Why are drugs calculated using molarities rather than concentration?
Molarity works in number of molecules per volume, rather than grams per volume. This is important for drug action becauses it is the number of molecules around the drug target that effects the action of the drug. Therefore you could have the same concentration of two drugs in grams/L but not have the same number of molecules of each drug.
How do most drugs interact with receptors?
Most bind irreversibly.
Binding of drugs to targets obeys the law of mass action. What does this mean? What is the consequences of this?
It's a law that states that, in a solution that is at dynamic equilibrium, the rate of a chemical reaction is proportional to the product of the masses of the reactants. Therefore the action of a drug (ligand) binding a receptor is affected by both the number of ligands and number of receptors.
ligand + receptor ligand-receptor complex
Do antagonists have intrinsic efficacy?
No - upon binding they are unable to create the conformational change which activates the receptor.
How can you measure how well a drug bind to its receptor (drug-receptor interactions)?
By binding of radioactively labelled ligands to cells or membranes prepared from cells. You can then measure how the proportion of bound receptors changes as drug concentration is increased.
What is Bmax a measure of?
The maximum binding capacity (all receptors bound with ligand) - if you know the concentration of drug used to reach the Bmax, you can work out the number of receptors present.
What is Kd a measure of?
It is the dissociation constant - a measure of the affinity of a drug for its receptor. It is the concentration of drug required to give 50% occupancy of the AVAILABLE receptors (i.e. half of Bmax).
Drug A has a Kd of 10^-9nM and drug b has a Kd of 10^-3mM. Which has the higher affinity?
Drug A - 50% of its receptors are occupied at a significantly lower concentration of the drug. Therefore it has a greater ability to bind to its receptor than drug B (higher affinity).
How does K(A) differ from K (d)?
K(A) is a measure of affinity like K(d) but has been determined by pharmocological methods rather than radiactive labelling of ligands.
At a 1nM concentration of a drug with a Kd of 1nM, what is the number of receptors bound (there are 100,000 receptors present)?
50,000: half of the available receptors because the concentration of the drug is equal to Kd (the concentration of the drug which gives 50% occupancy of receptors).