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4 Drug interaction(^1) c
a
b
B
Fr
actional concentration of drug B
Fractional concentration of drug A
1
A
C
Figure 4.1.Isobolograms with lines of equal activity: (a) additive; (b) synergistic;
(c) antagonistic (see text for explanation).
Potentiation
Potentiation results from an interaction between two drugs in which one drug has
no independent action of its own, yet their combined effect is greater than that of the
active drug alone. For example, probenecid reduces the renal excretion of penicillin,
such that the effect of a dose of penicillin is enhanced without itself having antibiotic
activity.
Synergism
Synergy occurs when the combined action of two drugs is greater than would be
expected from purely an additive effect. Often this is because the drugs exert similar
effects, but through different mechanisms. Propofol and remifentanil act synergis-
tically when used to maintain anaesthesia.
Isobologram
The nature of interactions between different agents may be studied by use of an
isobologram (Greekisos,equal;bolus,effect). An isobologram describes the com-
bined effect of two different drugs. Consider two drugs A and B, each of which indi-
vidually produce the required effect at concentrations a and b mmol.lā1,respectively.
Acurve may be constructed from the fractional concentrations of each, plotted on
the x- and y-axes, that produce the target effect. A straight line from 1 on the x-axis
(drug A) to 1 on the y-axis (drug B) describes a purely additive effect where half the
concentrations of each drug combine to produce the original target effect. When
the resultant curve is not linear, some interaction between the drugs is occurring.
Consider what happens when we have a concentration a/2 of drug A. If we can com-
bine it with a concentration b/2 of drug B and the result is the same as with either