Session 8 Flashcards
What is affinity?
Ability to bind to the receptor
How do you calculate molarity?
g/L/molecular weight
Define efficacy
How good a compound is at responding (efficacy is the maximum effect that a drug can produce).
It includes the intrinsic efficacy and the cell/tissue dependent factors
What is drug action governed by?
Affinity and intrinsic efficacy
Describe agonists and antagonists in terms of affinity and intrinsic efficacy
Agonists - have both affinity and intrinsic efficacy
Antagonists - have only affinity
How can drug-receptor interactions when binding be measured?
Binding of a radioligand to cells or membranes are prepared from cells. Low [ligand] = low binding
High [ligand] = high binding
What is the B max?
What information can we glean from this value?
B max is the binding capacity of the compound. Tells us about the receptor number.
What is Kd?
The dissociation constant –> a lower Kd means higher affinity
Concentration needed to occupy 50% of receptors
Define concentration and dose
Concentration = conc of drug as site of action e.g. in cells/tissues Dose = conc of drug at site of action unknown e.g. to patient in mg or mg/kg
What is EC50?
The effective concentration giving 50% of the maximal response. It’s a measure of agonist potency and depends on both intrinsic efficacy and affinity.
Define selectivity
The tendency of the drug to have effects other than it’s intended effect.
What is IC50?
Inhibitory concentration that gives 50% of the maximum inhibition
What is the use of a receptor reserve?
It makes the cell/tissue more sensitive to the stimulant, allowing for a response at smaller concentrations
What does changing the number of receptors on a cell do?
Alters the potency
What is a partial agonist?
A compound that does not produce a maximal response even if all the receptors are being used.
The EC50 of a partial agonist = it’s Kd
Give an example of partial agonists
Opiods - used for pain relief/recreationally but can lead to respiratory depression (bit not good)
Can partial agonists become agonists?
Yes. If there is an increase in the number of receptors then although there is low efficacy there will be sufficient bindings to ensure a full response
What does maximal response indicate?
Intrinsic activity
What are reversible competitive antagonists?
Reversible competitive antagonism (commonest and most important in therapeutics) - depends on dynamic equilibrium between ligands and receptors. The inhibition is surmountable (overcome) by addition of more agonist.
What is irreversible competitive antagonism?
Irreversible competitive antagonism – occurs when the antagonist dissociates very slowly or not at all (e.g. because of a covalent bond between ligand and receptor). The inhibition is non- surmountable.
What is non-competitive antagonism?
Non-competitive antagonism - generally a post-receptor or allosteric event.
What effect does a reversible competitive antagonist have on an agonist concentration-response curve?
Reversible competitive antagonists cause a parallel shift to the right of the agonist concentration-response curve
What effect does an irreversible competitive antagonist have on an agonist concentration-response curve?
Irreversible competitive antagonists cause a parallel shift to the right of the agonist concentration-response curve (at higher concentrations suppress the maximal response).
Define potency
Potency is the amount of a drug needed for it to have the maximum effect. This is a combination of both affinity and efficacy
What is homologous desensitisation?
Homologous desensitisation – the process by which only the signal from the stimulated receptor is reduced.
What is heterologous desensitisation?
Heterologous desensitisation – the process when receptors for other agonists become less effective even when only one has been continuously stimulated.
