therapeutic use. This process can be reversed when free drug is excreted from
the body. The drug molecule is released from the protein and it becomes free
drug and can be absorbed for use. Drugs affect areas of the body with good
blood supply first, such as the heart, liver, kidney, and brain and then flow to
areas with less blood supply, such as muscles and fat.
Drugs accumulate in an area of the body and form a reservoir by binding to
tissues. This is referred to as pooling. There are two types of pooling. These are
protein binding—when a drug binds to plasma proteins, and tissue binding—fat
soluble drugs are stored in adipose (fat) tissue. Inderal (propranolol) is a heart
medication that is highly bound to and only about 7% of free drug is available
for use at a time. Thiopental (pentothal) is an anesthetic agent that is stored in
fat tissue. In addition, some drugs, such as the antibiotic Tetracycline like to be
stored in bones which can interfere with growth of fetal skeletal tissues and can
discolor teeth if given to children under eight years of age.
Distribution of drugs is affected by three factors.Level of Plasma Protein
A low level of plasma protein and albumin might not provide enough binding
sites for drug particles. This results in a buildup of drugs which can reach a toxic
level. This happens when there is liver or kidney disease or if the patient is mal-
nourished resulting in low albumin levels (hypoalbuminemia). The elderly are
prone to hypoalbuminemia. Healthcare professionals should monitor a patient’s
plasma protein and albumin levels and the protein-binding percentage of all
drugs before administering drugs to the patient.Bloodflow
There must be adequate bloodflow to target areas of the body; otherwise, insuf-
ficient drug particles will reach affected parts of the body. Drugs can also be
stored in fat, bones, muscle, and the eyes. Drugs that accumulate in fat are called
lipid soluble and remain for about three hours because there is low blood flow
in fat tissue.
The body also has a blood–brain barrier that enables only lipid soluble
drugs—such as general anesthetics and barbiturates—into the brain and cere-
bral spinal fluid (CSF). The only way for nonlipid soluble drugs to enter the
brain is if they are instilled intrathecally, that is, injected directly into the CSF,
bypassing the blood-brain barrier.Competing Drugs
Two drugs administered simultaneously might compete for the same binding
sites making some drug particles unable to find a binding site. The result is an(^30) CHAPTER 2 Drug Action and Drug Interactions