Drug Design relating to Properties (Nodulin) Flashcards
What are the general tactics of Metabolism Guided Drug Design?
Removal of soft spots - overcoming toxicity, increasing duration of action
Addition of soft spots - decrease half-life
Modulating steric and electronic factors - increase duration of action
Reducing lipophilicity - increase duration of action
What is Emax?
The maximum effect that has been reached
How do you work out EC50?
Half of the maximal effective concentration.
The higher the EC50 is, the lower the potency
How do you convert between Molar, milimolar, micromolar and picomolar?
1 M = 1,000 mM
1 mM = 1,000 uM
1 uM = 1,000,000 pM
What are the types of agonists and antagonists?
Complete agonists usually bind directly to endogenous receptor, bringing about a full response.
Partial agonists usually bind indirectly, promoting the binding of the endogenous ligand, producing a delayed or lower response.
Inverse agonists produce the opposite effect as the endogenous ligand.
Competitive antagonist bind to directly to the endogenous receptor, while non-competitive antagonist bind to an allosteric site.
Irreversible antagonist bind strongly with covalent bonds to the receptor and cannot be displaced.
What is pA2?
pA2 is an indirect measurement of an antagonist’s affinity.
pA2 = pAx + log(x-1)
where pAx is the negative log of the concentration of the antagonist, and x is the concentration-ratio (ratio of concentration of agonist that gives the same response in the presence and absence of the antagonist).
Concentration ratio (x) = EC50 with antagonist / EC50 without antagonist.
What is the difference between EC50 and ED50?
EC50 describes the effective concentration needed for a response, while ED50 describes the effective dose needed. Concentration and dose can have different levels due to the absorption of the drug after administration.
