C H A P T E R 2
Drugs and the body
17
Drug–carrier molecules (ion transporters)
interactions
Some drugs are transported inside the cell through an
ion transporter or an ion molecule. Ion or drug mole
cules that are not ipid soluble enough to be transported
across the biological cell membrane must be transported.
Examples of transporters include those that transport
glucose and move sodium and calcium ions out of cells.
Other important transporters include those that are
involved in the uptake of chemicals acting at nerve ter
minals, such as noradrenaline, 5-hydroxytryptamine
(5-HT, serotonin) and glutamate.
Drug–ion channel interactions
Ion channels are selective pores in the cell membrane
that allow the movement of ions in and out of the cell.
Some drugs will block these channels, which ultimately
interferes with ion transport and causes an altered phys
iological response. Drugs working in this way include
nifedipine, verapamil and lignocaine.
Drug–receptor interactions
Receptors are target molecules with which a drug
molecule has to combine to illicit a specific effect. The
drug molecule combines with and affects the function
of the protein molecule thus producing its effect. This
is called
receptor activation
. However, occupation of
a receptor by a drug molecule may or may not result
in
activation
of the receptor. The tendency of a drug to
bind to receptors is governed by
affinity,
whereas the
tendency for a drug molecule, once bound, to activate
the receptor is denoted by its
efficacy
. More importantly,
in order to produce a therapeutic effect, a drug molecule
must act
selectively
on particular cells and tissues. This
means that individual drug molecules will only bind to
certain targets and individual targets will only recog
nise certain classes of drug molecules.
Receptor sites
Many drugs are thought to act at specific areas on cell
membranes called
receptor sites
. The receptor sites react
with certain endogenous chemicals (
transmitters
and
hormones) to cause an effect within the cell. In many
situations, nearby enzymes break down the reacting
chemicals and make the receptor site ready for further
stimulation.
To better understand this process, think of how
a key works in a lock. The specific chemical (the key)
approaches a cell membrane and finds a perfect fit (the
lock) at a receptor site (Figure 2.1). The interaction
between the chemical and the receptor site affects
enzyme systems within the cell. The activated enzyme
systems then produce certain effects, such as increased
or decreased cellular activity, changes in cell membrane
permeability or alterations in cellular metabolism.
Some drugs interact directly with receptor sites
to cause the same activity that natural or endogenous
chemicals would cause at that site. These drugs are called
agonists
(Figure 2.1A). For example, insulin reacts with
specific insulin-receptor sites to change cell membrane
permeability, thus promoting the movement of glucose
into the cell. Therefore, agonists are drug molecules
that bind to receptors
(affinity
) and once bound activate
receptors (
efficacy
). This ability to initiate a response
after binding with the receptor is referred to as intrinsic
activity.
Some drugs bind with receptor sites to block normal
stimulation, producing no effect. These drugs are called
antagonists
(Figure 2.1C)
.
Antagonists
are drug mole
cules that bind to receptors (
affinity
) without causing
activation
(efficacy
). For example, curare (a drug used
on the tips of spears by inhabitants of the Amazon basin
to paralyse prey and cause death) occupies receptor sites
for acetylcholine, which is necessary for muscle contrac
tion and movement. Curare prevents muscle stimulation,
causing paralysis. Curare is said to be a
competitive
antagonist
of acetylcholine (Figure 2.1B).
Still other drugs react with specific receptor sites
on a cell and, by reacting there, prevent the reaction of
another chemical with a different receptor site on that
cell. Such drugs are called
non-competitive antagonists
(Figure 2.1C). For some drugs, the actual mechanisms of
action are unknown. Speculation exists, however, that
many drugs use receptor-site mechanisms to bring about
their effects.
Other drugs act to prevent the breakdown of natural
chemicals that are stimulating the receptor site. For
example, monoamine oxidase (MAO) inhibitors block
the breakdown of noradrenaline by the enzyme MAO.
(Normally, MAO breaks down noradrenaline, removes
it from the receptor site and recycles the components to
form new noradrenaline.) The blocking action of MAO
inhibitors allows noradrenaline to stay on the receptor
site, stimulating the cell longer and leading to prolonged
noradrenaline effects. Those effects can be therapeutic
(e.g. relieving depression) or adverse (e.g. increasing heart
rate and blood pressure). Selective serotonin reuptake
inhibitors (SSRIs) work similarly to MAO inhibitors in
that they also exert a blocking action. Specifically, they
block removal of serotonin from receptor sites. This
action leads to prolonged stimulation of certain brain
cells, which is thought to provide relief from depression.
Loss of receptor response
Prolonged exposure of receptors to drug molecules can
result in gradual decrease in the number of receptors.
This is often referred to as
desensitisation
and
tachy-
phylaxis
. There are several mechanisms that give rise
