a. Excretion is the process of eliminating a drug or its metabolites from the body.
The major organ of excretion is the kidney. Secondary routes of excretion are hepatic
(liver), through the bile into the feces, lungs, saliva, sweat, and breast milk.
b. The inability of a patient to excrete drugs and other waste can be life
threatening. The elimination of drugs through sweat, saliva, and the lungs is of minor
interest in this subcourse. Of course, the excretion of drugs in breast milk is of concern
to mothers who breast-feed their infants. As a rule, drugs that are weakly basic are
more likely to be excreted in breast milk, because the milk is slightly acidic; therefore,
the basic drugs are more soluble in breast milk.
c. Patients who have limited liver and kidney function usually require lower
doses of medication. This is because more of the drug tends to stay in the body.
3-14. MECHANISMS OF DRUG ACTION
a. Receptor Site Theory. A drug that finally enters a cell may produce an
effect. It is able to produce this effect by a variety of complex biochemical processes.
Most of the processes can be simplified into one explanation of the mechanism of drug
action known as the receptor-site or "lock and key" theory. This theory states that a
drug (the key) combines with a receptor-site (the lock) to produce a pharmacological
effect. Drugs that will fit into the receptor-site are said to have an "affinity" for that
receptor-site. Only drugs that fit into the receptor-site will produce a pharmacological
response. Figure 3-5 visually represents the receptor-site theory.
b. Chemical Structure Activity Relationship. As a review, drug molecules
have specific chemical structures. The chemical structure of a drug will determine if a
drug molecule (the key) will fit into the receptor-site (the lock) and produce a
pharmacological effect. For example, whether the hydroxyl (OH-) group is on the left or
right side of the molecule or is at a 520 angle with the molecule can determine whether
the "key" will fit the "lock." This is referred to as chemical structure activity relationship.
From this, we can say that drugs that are similar in composition and chemical structure
may have similar effects. The chemical structure of a drug can be altered with no effect
upon the pharmacological effect the drug produces. However, the change in the
chemical structure of the drug molecule can increase or decrease its side effects.
Further, the modification of a drug molecule can influence its pharmacological actions.
Therefore, the modification of a drug's molecular structure can result in the formation of
a drug that can produce a desired pharmacological effect with a significantly lower dose
and with an accompanying decrease in undesired side effects.