Sites of Action of drug

Potential Targets of Drug Action
Drugs are designed to exert a selective
influence on vital processes in order to
alleviate or eliminate symptoms of disease.
The smallest basic unit of an organism
is the cell. The outer cell membrane,
or plasmalemma, effectively demarcates
the cell from its surroundings,
thus permitting a large degree of internal
autonomy. Embedded in the plasmalemma
are transport proteins that
serve to mediate controlled metabolic
exchange with the cellular environment.
These include energy-consuming
pumps (e.g., Na, K-ATPase), carriers
(e.g., for Na/glucose-cotransport,),
and ion channels e.g., for sodium or calcium .
Functional coordination between
single cells is a prerequisite for viability
of the organism, hence also for the survival
of individual cells. Cell functions
are regulated by means of messenger
substances for the transfer of information.
Included among these are “transmitters”
released from nerves, which
the cell is able to recognize with the
help of specialized membrane binding
sites or receptors. Hormones secreted
by endocrine glands into the blood, then
into the extracellular fluid, represent
another class of chemical signals. Finally,
signalling substances can originate
from neighboring cells, e.g., prostaglandins
and cytokines.
The effect of a drug frequently results
from interference with cellular
function. Receptors for the recognition
of endogenous transmitters are obvious
sites of drug action (receptor agonists
and antagonists, p. 60). Altered activity
of transport systems affects cell function
(e.g., cardiac glycosides,;
loop diuretics,; calcium-antagonists,).
Drugs may also directly
interfere with intracellular metabolic
processes, for instance by inhibiting
(phosphodiesterase inhibitors,)
or activating (organic nitrates,)
an enzyme .
In contrast to drugs acting from the
outside on cell membrane constituents,
agents acting in the cell’s interior need
to penetrate the cell membrane.
The cell membrane basically consists
of a phospholipid bilayer (80Å =
8 nm in thickness) in which are embedded
proteins (integral membrane proteins,
such as receptors and transport
molecules). Phospholipid molecules
contain two long-chain fatty acids in ester
linkage with two of the three hydroxyl
groups of glycerol. Bound to the
third hydroxyl group is phosphoric acid,
which, in turn, carries a further residue,
e.g., choline, (phosphatidylcholine = lecithin),
the amino acid serine (phosphatidylserine)
or the cyclic polyhydric alcohol
inositol (phosphatidylinositol). In
terms of solubility, phospholipids are
amphiphilic: the tail region containing
the apolar fatty acid chains is lipophilic,
the remainder – the polar head – is hydrophilic.
By virtue of these properties,
phospholipids aggregate spontaneously
into a bilayer in an aqueous medium,
their polar heads directed outwards into
the aqueous medium, the fatty acid
chains facing each other and projecting
into the inside of the membrane.
The hydrophobic interior of the
phospholipid membrane constitutes a
diffusion barrier virtually impermeable
for charged particles. Apolar particles,
however, penetrate the membrane
easily. This is of major importance with
respect to the absorption, distribution,
and elimination of drugs.