Pharmacology for Anaesthesia and Intensive Care

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Section IBasic principles

x/2

Fractional Response

1

0.5

Agonist

Agonist + non-competitive

inhibitor

log (K log (agonist concentration)

D)

x

(b)

Agonist

LOG DR

LOG DR

% Response

100

75

50

25

LOG DR

log (agonist concentration)

Agonist + competitive

inhibitor

(a)

Figure 3.4.Reversible antagonists.(a)competitive inhibition.Notethe parallel shift to

the right in the presence of competitive inhibitor, with preservation of maximum response.

DR represents dose-ratio (see text). (b)non-competitive inhibition.This time maximum

possible response is given as a fraction. In the presence of the non-competitive inhibitor the

curve is not shifted to the right, but the maximum obtainable response is reduced. KDis the

dissociation constant and is unaltered by the inhibitor.

As a general principle, first postulated by Bowman, weaker antagonists at the

neuromuscular junction have a more rapid onset of action. This is because they

are given in a higher dose for the same maximal effect so that more molecules are

available to occupy receptors, and the receptor occupancy required for full effect is

achieved more rapidly. Rocuronium, a non-depolarizing muscle relaxant, has only