C H A P T E R 1 6
Anti-inflammatory, antiarthritis and related agents
243
this reaction can lead to death in aspirin-sensitive asth-
matics; bleeding abnormalities
because of the changes
in platelet aggregation associated with these drugs
;
impaired renal function
because the drug is excreted in
the urine
; chickenpox or influenza
because of the risk
of Reye’s syndrome in children and teenagers
; surgery
or other invasive procedures scheduled within 1 week
because of the risk of increased bleeding
; and pregnancy
or breastfeeding
because of the potential adverse effects
on the neonate or mother
.
Adverse effects
The adverse effects associated with salicylates may be
the result of direct drug effects on the stomach (nausea,
dyspepsia, heartburn, epigastric discomfort) and on
clotting systems (blood loss, bleeding abnormalities).
Salicylism
can occur with high levels of aspirin; dizzi
ness, ringing in the ears, difficulty hearing, nausea,
vomiting, diarrhoea, mental confusion and lassitude can
occur. Acute salicylate toxicity may occur at doses of
20 to 25 g in adults or 4 g in children. Signs of salicylate
toxicity include hyperpnoea, tachypnoea, haemorrhage,
excitement, confusion, pulmonary oedema, convulsions,
tetany, metabolic acidosis, fever, coma and cardiovascu-
lar, renal and respiratory collapse.
Clinically important drug–drug interactions
The salicylates interact with many other drugs, pri-
marily because of alterations in absorption, effects on
Leukotrienes
Chemotaxis,
activation of neutrophils
Phagocytosis
Prostaglandins
Release of arachidonic acid
Release of
histamine
Exposure of
cell membrane
Activation of
Hageman factor
Prekallikrein Active kallikrein
Kininogen Bradykinin
Tissue injury
Vasodilation
Increased
capillary
permeability
Gold salts
work here
Etanercept,
anakinra
work here
Antihistamines
work here
Salicylates,
NSAIDs
work here
Corticosteroids
work here
FIGURE 16.1
Sites of action of anti-inflammatory agents.
Rheumatoid arthritis is a chronic, systemic disease
that affects people of all ages. It is considered to be
an autoimmune disease. People with rheumatoid
arthritis have high levels of rheumatoid factor (RF),
an antibody to immunoglobulin G (IgG). RF interacts
with circulating IgG to form immune complexes, which
tend to deposit in the synovial fluid of joints, as well as
in the eye and other small vessels. The formation of the
immune complex activates complement and precipitates
an inflammatory reaction. During the immune reaction,
lysosomal enzymes are released that destroy the tissues
surrounding the joint. This destruction of normal tissue
causes a further inflammatory reaction, and a cycle of
destruction and inflammation ensues. Over time, the
joint becomes severely damaged and the synovial space
fills with scar tissue.
■■
BOX 16.3
Pathophysiology of rheumatoid
arthritis
