20 Drug Interactions

Anthony W. FoxandAnne-Ruth van Troostenburg de Bruyn

20.1 Definition

A drug interaction is an effect observed with two or
more drugs, which is not seen with one drug alone.
The effect can be qualitative or quantitative. Drug
interactions can constitute clinical hazard or be
exploited for therapeutic benefit.
In modern clinical settings, patients often
receive multiple drugs. Every physician will be
aware of the benefits of pharmacodynamic interac-
tions of medications – such as additional effects on
blood pressure when combining ACE inhibitors,
calcium antagonists or beta blockers to treat hyper-
tension. The interactions of these drugs result in
additional blood pressure lowering effect, which
can be both wanted or unwanted in its magnitude.
Equally, all physicians will be aware of the poten-
tial for adverse effects of commonly used drugs,
such as warfarin, when another drug is introduced
at the same time. Care needs to be taken, in both
cases, when either the target of the mechanism of
action is the same for two drugs, or one drug alters
the pharmacokinetics of the other.
The purpose of this chapter is to offer a descrip-
tion of drug interactions in a systematic manner. It
is impossible to remember all drug interactions,
and information technology and ready-reference
manuals should always be used. But, within the

realm of pharmaceutical medicine, additional

aspects that must be borne in mind are to under-

stand how interactions may be described and quan-

tified on paper, whether in product labeling,

regulatory submissions or scientific reports.

20.2 Description and

quantitation of drug

interactions

Drug interactions may be described asadditive,

antagonistic or synergistic (or potentiating).

These three categories are regardless of whether

the underlying mechanism is pharmacodynamic or

pharmacokinetic in nature.

Drug interactions may be quantitated and illu-

strated usingisobolograms.An isolobologram is

simply a method of illustrating data with three

variables in two dimensions, that is on the surface

of a piece of paper. This form of plotting should not

be unfamiliar. Analogous examples of such plots

are found (three dimensions) on topographical

maps (latitude, longitude and elevation above sea

level) and meteorological charts (e.g. latitude,

longitude and barometric pressure); in both cases

the third variable is shown by the contours. In the

Principles and Practice of Pharmaceutical Medicine, 2nd Edition Edited by L. D. Edwards, A. J. Fletcher, A. W. Fox and P. D. Stonier
#2007 John Wiley & Sons, Ltd ISBN: 978-0-470-09313-9