McKenna's Pharmacology for Nursing, 2e

C H A P T E R 1 6  Anti-inflammatory, antiarthritis and related agents 243

Tissue injury

Antihistamines work here

Exposure of cell membrane

Release of histamine

Increased capillary permeability

Vasodilation

Activation of Hageman factor

Prekallikrein Active kallikrein

Kininogen Bradykinin

Corticosteroids work here

Release of arachidonic acid

Salicylates, NSAIDs work here

Etanercept, anakinra work here

Prostaglandins

Leukotrienes

Chemotaxis, activation of neutrophils

Gold salts work here

Phagocytosis

FIGURE 16.1  Sites of action of anti-inflammatory agents.

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

■■ BOX 16.3  Pathophysiology of rheumatoid arthritis

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 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.