Additive Effects, Synergism & Potentiation
When two or more drugs are given concurrently that produce the same
biological effect, the resulting effect generally follows one of three
patterns--additive effect, synergism, or potentiation.
Additive effects are the simplest case of combined drug action: the effects
of the drugs simply summate. If a dose of Drug-A that produces 50% of the
maximum response is given concurrently with a dose of Drug-B that produces
50% of the maximum response, then the maximum response is produced. If
a dose of Drug-A that produces 25% of the maximum response is combined
with a dose of Drug-B that produces 50% of the maximum response, then 75%
of the maximum response is produced. This simple algebraic summation of
effects is expected for full agonists; the situation is more complex for
partial agonists and inverse agonists.
Another way of viewing addictive effects is to consider the effect of
a competitive antagonist. If a fixed dose of a competitive antagonist is
given, then the agonist dose-response curve is shifted to the right. If
a fixed dose of a full agonist is given, then the dose-response curve for
the second agonist should be shifted to the left.
Synergism is said to occur when the combined effects of two agonists exceed
that predicted by the individual actions of these compounds (i.e., the
resulting effect is more than additive). Isoboles are constructed for drug
concentrations producing some constant effect, usually the ED50.
If the effects of the two drugs are additive, the slope of the resulting
plot is -1.
The term potentiation is used differently by various investigators.
Some pharmacologists use potentiation interchangably with synergism
to describe a greater than additive effect (e.g., Tallarida & Jacob,
1979). Others (e.g., Palfai & Jankiewicz, 1997) use potentiation
to describe what might better be termed response enabling. In this
situation the effect is only present when two compounds act concurrently.
Copyright 1999 Michael A. Bozarth
This page was last updated 04 November 1999 12:07 EDT
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