Drug Antagonism

Question 1

What is the Equation involving PA2

Answer 1

PA2 = - log[B] r=2

Question 2

Why do we use the PA2 equation

Answer 2

It allows us to compare antagonists, even if we don’t know the mechanism that they work with

Question 3

What does this imply if the mechanism of actions turns out to be reversible competitive inhibition?

Answer 3

For this case we know r = 1 + [B]/Kb
And we know r = 2
Thus… PA2 = log Kb

Question 4

Name mechanisms that the receptor is not involved but through which the agonists acts

Answer 4

A) chemical antagonism- antagonist binds directly with substance being antagonized
B) functional and physiological antagonism- the antagonist is an agonist that produces the opposite biological effect to the substance being antagonised
C) pharmacokinetic antagonism-antagonist reduces concentration of active drug at site of action
D) indirect antagonism- acts as a 2nd downstream site which links the action of the agonist to the final response observed

Question 5

Example of chemical antagonism

Answer 5

Herparin (makes it harder for clots to form) binds to protamine sulphate

Question 6

Example of functional/physiological antagonism

Answer 6

when the breakdown of PIP2 produces IP3 which then increases the calcium concentration in the cell cytoplasm …camp mechanism

Question 7

example of Pharmacokinetic antagonism

Answer 7

Phenobarbitone if given will up regulate the enzymes that metabolize warfarin -anticoagulant.

Question 8

Example of indirect antagonism

Answer 8

Verpamil ( calcium channel blocker ) will bind to the Ca receptors and block the influx of Ca, needed for smooth muscle contraction and hence reduce the contractile response to ACh