Adverse Drug Effects IV

Type 2, cytotoxic reaction. Drugantibody
(IgG) complexes adhere to the
surface of blood cells, where either circulating
drug molecules or complexes already
formed in blood accumulate.
These complexes mediate the activation
of complement, a family of proteins that
circulate in the blood in an inactive
form, but can be activated in a cascadelike
succession by an appropriate stimulus.
“Activated complement” normally
directed against microorganisms, can
destroy the cell membranes and thereby
cause cell death; it also promotes phagocytosis,
attracts neutrophil granulocytes
(chemotaxis), and stimulates other
inflammatory responses. Activation
of complement on blood cells results in
their destruction, evidenced by hemolytic
anemia, agranulocytosis, and
thrombocytopenia.
Type 3, immune complex vasculitis
(serum sickness, Arthus reaction).
Drug-antibody complexes precipitate on
vascular walls, complement is activated,
and an inflammatory reaction is triggered.
Attracted neutrophils, in a futile
attempt to phagocytose the complexes,
liberate lysosomal enzymes that damage
the vascular walls
. Symptoms may include fever,
exanthema, swelling of lymph
nodes, arthritis, nephritis, and neuropathy.
Type 4, contact dermatitis. A cutaneously
applied drug is bound to the
surface of T-lymphocytes directed specifically
against it. The lymphocytes release
signal molecules (lymphokines)
into their vicinity that activate macrophages
and provoke an inflammatory
reaction.