18
P A R T 1
Introduction to nursing pharmacology
to this phenomenon. A change in receptors or loss of
receptors can develop when a drug is given repeatedly
or continuously. Prolonged exposure to an
agonist
drug
can often result in a gradual decrease in the number
of receptors expressed on the cell’s surface or
receptor
downregulation.
This has often been shown for
β
adren
ergic receptors. The vanishing receptors are taken into
the cells by
endocytosis
. Whereas prolonged use of an
antagonist
drug can result in r
eceptor upregulation
.
Upregulation of receptor numbers is an increase in
the number of receptors on the surface of target cells,
making the cells more sensitive to a hormone or another
agent.
Selective toxicity
Ideally, all chemotherapeutic agents would act only
on receptors, structures or enzyme systems that are
essential for the life of a pathogen or neoplastic cell
and would not affect healthy cells. The ability of a
drug to attack only those systems found in foreign cells
is known as
selective toxicity
. Penicillin, an antibiotic
used to treat bacterial infections, has selective toxicity.
It affects an enzyme system unique to bacteria, causing
bacterial cell death without disrupting normal human
cell functioning.
Unfortunately, most other chemotherapeutic agents
also destroy normal human cells, causing many of the
adverse effects associated with antipathogen and anti
neoplastic chemotherapy. Cells that reproduce or are
replaced rapidly (e.g. bone marrow cells, gastrointestinal
[GI] cells, hair follicles) are more easily affected by these
agents. Consequently, the goal of many chemotherapeu
tic regimens is to deliver a dose that will be toxic to the
invading cells yet cause the lowest toxic effect to the host.
Drug A: An agonist
Drug A: An agonist
Drug A: An agonist
that binds to receptor
sites and produces an
effect
Drug B: Cannot bind
to receptor sites
on this cell and
produces no
effect
Drug D: A competitive
antagonist of Drug A
that binds to different
receptor sites from
Drug A but still prevents
Drug A from binding
Drug C: An antagonist
of Drug A that binds
to the same receptor
sites as Drug A and
prevents Drug A
from binding
C.
Non-competitive antagonism
B.
Competitive antagonism
A.
Agonist interaction with receptor site on cell
Molecule of Drug D
bound to receptor site
different from receptor
site for Drug A
Molecule of Drug A
bound to receptor site
Molecule of Drug C
bound to receptor site
Unoccupied receptor site
for Drug A
FIGURE 2.1
Receptor theory of drug action.
A.
Agonist interaction with receptor site
on cell. Molecules of drug A react with
specific receptor sites on cells of effector
organs and change the cells’ activity.
B.
Competitive antagonism. Drug A and
drug C have an affinity for the same
receptor sites and compete for these sites;
drug C has a greater affinity, occupies
more of the sites and antagonises drug A.
C.
Non competitive antagonism. Drug D
reacts with a receptor site that is different
from the receptor site for drug A but still
somehow prevents drug A from binding
with its receptor sites. Drugs that act
by inhibiting enzymes can be pictured
as acting similarly to the receptor site
antagonists illustrated in panels B and C.
Enzyme inhibitors block the binding of
molecules of normal substrate to active
sites on the enzyme.
