Quantification of Drug Action III

Concentration-Effect Relationship (A)
The relationship between the concentration
of a drug and its effect is determined
in order to define the range of active
drug concentrations (potency) and
the maximum possible effect (efficacy).
On the basis of these parameters, differences
between drugs can be quantified.
As a rule, the therapeutic effect or toxic
action depends critically on the response
of a single organ or a limited
number of organs, e.g., blood flow is affected
by a change in vascular luminal
width. By isolating critical organs or tissues
from a larger functional system,
these actions can be studied with more
accuracy; for instance, vasoconstrictor
agents can be examined in isolated
preparations from different regions of
the vascular tree, e.g., the portal or
saphenous vein, or the mesenteric, coronary,
or basilar artery. In many cases,
isolated organs or organ parts can be
kept viable for hours in an appropriate
nutrient medium sufficiently supplied
with oxygen and held at a suitable temperature.
Responses of the preparation to a
physiological or pharmacological stimulus
can be determined by a suitable recording
apparatus. Thus, narrowing of a
blood vessel is recorded with the help of
two clamps by which the vessel is suspended
under tension.
Experimentation on isolated organs
offers several advantages:
1. The drug concentration in the tissue
is usually known.
2. Reduced complexity and ease of relating
stimulus and effect.
3. It is possible to circumvent compensatory
responses that may partially
cancel the primary effect in the intact
organism — e.g., the heart rate increasing
action of norepinephrine
cannot be demonstrated in the intact
organism, because a simultaneous
rise in blood pressure elicits a counter-
regulatory reflex that slows cardiac
rate.
4. The ability to examine a drug effect
over its full rage of intensities — e.g.,
it would be impossible in the intact
organism to follow negative chronotropic
effects to the point of cardiac
arrest.