Adverse Drug Effects III

Drug Allergy
The immune system normally functions
to rid the organism of invading foreign
particles, such as bacteria. Immune responses
can occur without appropriate
cause or with exaggerated intensity and
may harm the organism, for instance,
when allergic reactions are caused by
drugs (active ingredient or pharmaceutical
excipients). Only a few drugs, e.g.
(heterologous) proteins, have a molecular
mass (> 10,000) large enough to act
as effective antigens or immunogens,
capable by themselves of initiating an
immune response. Most drugs or their
metabolites (so-called haptens) must
first be converted to an antigen by linkage
to a body protein. In the case of penicillin
G, a cleavage product (penicilloyl
residue) probably undergoes covalent
binding to protein. During initial contact
with the drug, the immune system
is sensitized: antigen-specific lymphocytes
of the T-type and B-type (antibody
formation) proliferate in lymphatic tissue
and some of them remain as socalled
memory cells. Usually, these processes
remain clinically silent. During
the second contact, antibodies are already
present and memory cells proliferate
rapidly. A detectable immune response,
the allergic reaction, occurs.
This can be of severe intensity, even at a
low dose of the antigen. Four types of
reactions can be distinguished:
Type 1, anaphylactic reaction.
Drug-specific antibodies of the IgE type
combine via their Fc moiety with receptors
on the surface of mast cells. Binding
of the drug provides the stimulus for the
release of histamine and other mediators.
In the most severe form, a lifethreatening
anaphylactic shock develops,
accompanied by hypotension,
bronchospasm (asthma attack), laryngeal
edema, urticaria, stimulation of gut
musculature, and spontaneous bowel
movements .