48 Section 1/ General Principles of PharmacologySide effects are also based on different
facet of action (or side effects unrelated to
its pharmacological or therapeutic effect).
All antihistaminics except few newer
compounds e.g. astemizole, terfenadine etc.
cause sedation which is unrelated to its
therapeutic action i.e. antiallergic action.
The history of pharmacology revealed that
certain drugs have been developed from the
observation of their side effects for example
sulfonamide produce hypoglycemia and
acidosis as side effect, which further gave an idea
for developing a new compound related to
sulfona-mide – sulfonylurea as hypoglycemic
agent and acetazolamide as diuretic.
TOXIC EFFECTSToxic effects develop due to excessive
pharmacological action of drug, which may
be due to overdose or continuous use of
drug for prolonged period.
The overdose toxicity occurs when the
high dose of drug is required for the specific
treatment or the drug is taken accidentally or
with the intention of suicide. The effects are
predictable and dose related. For example
delirium by the use of atropine and respiratory
failure by morphine occur due to their
overdoses. The well known antitubercular
drug, streptomycin causes vestibular damage
and deafness on prolonged use.
DRUG ALLERGY AND IDIOSYNCRASYHYPERSENSITIVITY (DRUG ALLERGY)
Drug allergy is a cell-mediated immune
reaction producing symptoms, which are
unrelated to the pharmacological effects of the
drug. It results from previous sensitization to
the drug itself or a particular chemical with
similar structure.
The B-lymphocytes, when exposed to
antigens mature into immunoglobulin
secreting cells after proliferation, which
often have the appearance of plasma cells.
The immunoglobulins (Ig) are secreted
by B-lymphocytes in the later stage of their
development into plasma cells. IgG, IgA,
IgM, IgE and IgD are immunoglobulins, out
of these IgG is the major one.
Based on the mechanism of immuno-
logical reactions, the allergic responses have
been divided into four categories:TYPE-I (ANAPHYLACTIC REACTION)
They are mediated by IgE antibodies. On
exposure to the drug, antigen and antibody
reaction takes place on mast cells and
basophils releasing various mediators e.g.
histamine, leukotrienes, 5 hydroxytryptamine
(5-HT), prostaglandins etc., which are
responsible for immediate immune reactions
like skin reaction, anaphylactic shock, asthma
etc. These reactions occur immediately after
challenge and are termed as immediate
hypersensitivity.TYPE-II (CYTOLYTIC REACTION;
DELAYED IGG/IGE MEDIATED)
These reactions are mediated by IgG and
IgE antibodies, which bind to the target cells
(cells in the circulating system). On
reexposure antigen-antibody reaction takes
place on the surface of these target cells and
cytolysis occur. Example are penicillin-