Biology Reference
In-Depth Information
(TW)—the range of concentrations over which the drug is both effective
and safe (see Figure 1-23). Our goal is to construct a model describing
how to achieve and maintain drug concentrations in this range.
Before we can begin to produce a model, we should consider the factors
influencing a drug's concentration in the bloodstream. These may be
roughly divided into factors controlling entry of the drug into the
bloodstream (absorption) and factors controlling its exit (elimination).
To consider absorption, we must first determine how the drug will be
introduced into the patient—orally, intravenously, intramuscularly,
transdermally (through the skin), or by inhalation. We must consider
whether the drug undergoes any physical or chemical changes during
administration. For example, is it a solid that must be dissolved in the
stomach or small intestine, or will it be introduced as a solution? We
must also consider the characteristics of the drug that will control how it
will be absorbed into the bloodstream. A fat-soluble molecule can
diffuse through intestinal cell membranes, whereas a charged or polar
molecule has to rely on transport proteins.
Once the drug has entered the bloodstream, we must consider how it
disperses through the body (distribution). For example, does the drug
bind to serum proteins, or does it circulate as a free drug? Distribution
also involves the drug's movement from the bloodstream to the tissue,
organ, or other area of the body where it has its effect—in the case of the
acetaminophen, your poor aching head.
While some acetaminophen will exit the bloodstream to reduce your
headache, the remainder will be removed by processes grouped under
the term elimination. Elimination may involve metabolism, the term for
any chemical reaction the drug undergoes in the body, as well as
excretion, which is usually the action of the kidneys.
C(t)
MTC
TW
MEC
t
0
Time
FIGURE 1-23.
Changes in serum drug concentration. The drug concentration changes because of the cumulative
effect of multiple doses and the elimination of the drug from the bloodstream. When maintained
within the therapeutic window, the drug concentration is both effective and safe.
