Module 2: Measurement In Pharmacology Flashcards
What are some examples of things that can change the number and/or function of drug targets?
Natural Ageing (ie beta adrenergic receptors in heart)
Disease (ie loss of dopamine receptors in Parkinson’s disease)
Toxins (ie cholera toxin targeting α subunit of GPCR)
What is the Law of Mass Action?
The rate of chemical reaction is proportional to the product of the concentration of reactants
What is Kd?
dissociation constant at equilibrium, measure of affinity. It is specific for that drug and that target only
How can Kd be calculated?
Kd= ([A]/Par) - [A]
What is the Hill-Langmuir equation?
Rearranged Kd equation:
Par= ([A])/Kd+[A]
The proportion of receptors occupied (Par) is dependent on what 2 factors?
Affinity of drug(Kd)
Concentration of drug ([A])
How is Kd experimentally determined?
The concentration of drug required to occupy 50% of receptors at equilibrium
What information can be given by the Schild equation?
Can determine the affinity of an introduced antagonist.
At a fixed concentration of antagonist [B], how much EXTRA agonist [A] must be added to elicit the original response?
The factor by which A must increase is r
What is Schild equation?
Log(r-1) = log[B] - log Kb
What is Bmax?
Number of receptors, usually reported as pmol/mg protein
How can binding assays identify if a drug has bound to a receptor?
Radiolabelled ligand.
Colorimetric do exist, but often affects the affinity.
What is a bioassay?
Estimation of concentration or potency of a substance by measurement of the biological response that it produces
What is the different between a bioassay and a binding assay?
bioassay is measuring a biological response. Binding assay looks specifically at binding to a receptor, not the reaction it elicits
What is Pasternak’s First Law of Research?
an assay is only as good as the choice of controls
What is the therapeutic index?
The maximum non-toxic dose divided by the minimum effective dose
