Pharmacodynamics

Sketch a graph of the Michaelis-Menten curve of reaction rate compared with substrate concentration

MM curve.

What is the Hill equation?

% = (100 x Conc) / (kd + Conc)

Used to work out the % of drug binding at a particular concentration.

Kd = dissociation constant

Draw a graph MM curve for a high affinity ligand and a low affinity ligand on the same graph

High and low affinity ligand.

Describe where a high affinity ligand will appear in comparison to a low affinity ligand on an MM curve

-High affinity will appear further left (towards the y axis)

-This is because it has a lower Kd

Describe the relationship between Kd and ligand affinity

The lower the Kd the higher the ligand affinity.

Draw a graph to show a high efficacy drug compared to a low efficacy drug with response % on the y axis and concentration on the x axis

efficacy graph.

What is the EC50 of a drug?

The concentration of drug that gives 50% of the maximum response.

Reference range of similar opioid drugs

Graph shows that the blue Etorphine likely has the highest affinity as it has a higher EC50 than the others.

What is the potency of a drug?

The relationship between the concentration (of the drug) and the efficacy.

-I.e. a higher potency = a higher efficacy at a lower drug concentration

How do you define a partial agonist and how is it shown on a graph?

-Has agonistic effects but never reaches 100% efficacy

-Shown on a graph by not reaching 100%

On what graph can you only truly measure a drugs affinity?

Binding curve (NOT Dose-response).

How can a partial agonist effect the activity of an agonist? What are the implications of this?

-If you prescribe a partial agonist before prescribing an agonist, the agonist will be competitively inhibited by the partial agonist as it is saturating the binding site

-This means that the agonist will never reach full efficacy as the partial agonist predominates until it becomes metabolised

What is the effect of a competitive antagonist?

Causes the original drug to reach Emax slower, but can still reach it with an increase in drug concentration as the drug outcompetes it.

-I.e. Shift the curve to the right

What is the effect of a non-competitive antagonist?

-The non-competitive antagonist binds to an alternate binding site the prevent the binding of the normal substrate and hence means it will never reach Emax

-Means the drug will never reach 100% response on the graph