Competitive and irreversible antagonists

This document was created by Alex Yartsev (dr.alex.yartsev@); if I have used your data or images and forgot to reference you, please email me.

Competitive and irreversible antagonists

COMPETITIVE (REVERSIBLE) ANTAGONISTS

100%

These can be overcome with a high enough concentration of agonist

With competitive antagonism, the amount of

50%

In absence of an antagonist

In presence of an

agonist needed to get the same response is greater, and the EC50 is shifted to the right.

competitive antagonist

The potential for a maximum effect

remains the same

Agonist concentration

(there is, after all, the same number of receptors to bind - its just that some of them have an antagonist latched onto them, and with a high enough concentration you will displace them all and get a maximum effect)

Effect

Effect

100% 50%

In absence of an antagonist

In presence of increasing doses of an irreversible antagonist

Agonist concentration

IRREVERSIBLE ANTAGONISTS

These drugs take some receptors completely out of the game. The favourite way of doing this is to

bind to the receptor in a covalent fashion.

This may mean that the remaining number of free receptors is uselessly low.

The maxiumum possible response is thus DECREASED.

... UNLESS! There are "Spare receptors".

Say there are 100 receptors and 50 effectors. So maybe you manage to irreversibly antagonize 50 of the receptors. So what? The redundant 50 receptors are still enough to activate 50 effectors, so if you then give an agonist drug it will still achieve the maximum effect. The dose-response curve will look as if no antagonist was given.

From "Goodman & Gilman's The Pharmacological Basis of Therapeutics" 11th ed by Brunton et al,and "Basic & Clinical Pharmacology" 11th ed. By Katzung et al

 ................
................

In order to avoid copyright disputes, this page is only a partial summary.

Google Online Preview   Download