accumulation of free drug that could reach toxic levels. Two drugs that are
highly protein bound—such as Coumadin (warfarin) and Inderal (propra-
nolol)—will compete for the protein sites. This can cause serious problems and
can result in toxic levels of one or both of the drugs when increased amounts of
free drug become available.
Abscesses, exudates, body glands, and tumors hinder the distribution of drugs
in the body. In addition, antibodies do not distribute well at abscess and exudates
sites. The placenta metabolizes some drugs making then inactive and thereby
protecting the fetus from drugs given to the mother. However, steroids, nar-
cotics, anesthetics, and some antibiotics can penetrate the placental barrier and
cause adverse effects to the fetus.
ELIMINATION
Drugs accumulate in a reservoir and are gradually absorbed and eventuallyelim-
inated by the body. This metabolism—called biotransformation—occurs in the
liver where enzymes inactivate a drug by changing it into more water-soluble
compounds that can be excreted from the body. Elimination occurs mainly
through the kidneys, although some drugs are also eliminated in bile, feces,
lungs, sweat, and breast milk.
Patients suffering from liver diseases are prone to drug toxicity because the
diseased liver no longer metabolizes the drug sufficiently to allow elimination
through the kidneys. The result is a buildup of the drug, which can eventually
lead to a toxic effect on the body.
The amount of time for half of the drug concentration to be eliminated from
the body is called the drug’s half-life and is a crucial measurement used to deter-
mine how often to administer a drug. Some drugs have a short half-life (less than
8 hours) while other drugs have a longer half-life (24 hours).
For example, Digoxin has a half-life of 36 hours. This means it takes 5 to
7 days before there is a steady state of Digoxin in the serum. This is referred
to as the steady state serum concentration and is the time it takes for the drug to
have a therapeutic effect.
Children and the elderly might be unable to absorb and/or eliminate drugs.
This can result in toxicity should additional doses be given before the previ-
ous does is eliminated from the body. Free drugs, water-soluble drugs, and
unchanged drugs are filtered by the kidneys and eliminated through urine.
Protein-bound drugs do not filter through the kidneys until the drug is released
from the protein.
The quantity of drugs that can be excreted by the kidneys is influenced by the
pH of the urine, which normally is between 4.5 and 8.0. Acidic urine (4.5) elimi-
CHAPTER 2 Drug Action and Drug Interactions^31