McKenna's Pharmacology for Nursing, 2e

C H A P T E R 1 6  Anti-inflammatory, antiarthritis and related agents 249

The evidence (continued)

BOX 16.4

stomach lining, regulation of blood clotting and water and salt balance in the kidney. The COX-2 inhibitors are thought to act only at sites of trauma and injury to more specifically block the inflammatory reaction. The adverse effects associated with most NSAIDs are related to blocking of both of these enzymes and changes in the functions that they influence—GI integ- rity, blood clotting and sodium and water balance. The COX-2 inhibitors are designed to affect only the activity of COX-2, the enzyme that becomes active in response to trauma and injury. They do not interfere with COX-1, which is needed for normal functioning of these systems. Consequently, these drugs should not have the associated adverse effects seen when both COX-1 and COX-2 are inhibited. Experience has shown that the COX-2 inhibitors still have some effect on these other functions, and people should still be evaluated for GI effects, changes in bleeding time and water retention. Recent studies suggest that they may block some pro- tective responses in the body, such as vasodilation and inhibited platelet clumping, which is protective if vessel narrowing or blockage occurs; blocking this effect could lead to cardiovascular problems. Box 16.5 summarises the actions and adverse effects of the COX-1 and COX-2 receptors. COX-1 Site of action Found in many tissues, important for homeostasis Effects • Converts arachidonic acid to inflammatory prostaglandins • Maintains renal function • Provides for gastric mucosa integrity • Promotes vascular haemostasis, increases bleeding • Autocrine effects causing fever Effects of blocking • Decreases swelling, pain, inflammation • Sodium retention, oedema, increased blood pressure • Gastrointestinal erosion, bleeding • Decreases fever ■■ BOX 16.5  Comparison of cyclooxygenase (COX) receptors Specialists treating people with chronic pain have petitioned to have the FDA return rofecoxib and valdecoxib to the market, citing people who could only obtain relief using those drugs. Some people only respond to these particular NSAIDs, and these specialists feel that people should have a choice, being informed of the risks, to continue their use to relieve pain. Clearly, more long-term studies are needed.The nurse may be asked about this

The NSAIDs are indicated for relief of the signs and symptoms of rheumatoid arthritis and osteoarthritis, for relief of mild to moderate pain, for treatment of primary dysmenorrhoea and for fever reduction. Pharmacokinetics The NSAIDs are rapidly absorbed from the GI tract, reaching peak levels in 1 to 3 hours. They are metabo- lised in the liver and excreted in the urine. NSAIDs cross the placenta and enters into breast milk. Therefore, they are not recommended during pregnancy and breastfeed- ing because of the potential adverse effects on the fetus or neonate. Contraindications and cautions • The NSAIDs are contraindicated in the presence of allergy to any NSAID or salicylate, and celecoxib is also contraindicated in the presence of allergy to sulfonamides. Additional contraindications are cardiovascular dysfunction or hypertension because of the varying effects of the prostaglandins ; peptic ulcer or known GI bleeding because of the potential to exacerbate the GI bleeding ; and pregnancy or breastfeeding because of potential adverse effects on controversy and what recommendations are in place by people who want relief from pain but really want to understand the risks to their health.To get a complete summary of the research, the report to the FDA, and current recommendations and research, go to www.fda.gov and click on NSAIDs under HotTopics on the right side of the page.This site is updated regularly and offers information geared to people and to healthcare professionals. COX-2 Site of action Induced by inflammatory stimuli at the site of inflammation Effects • Increases pain, inflammation • Vasodilates • Blocks platelet clumping Effects of blocking • Decreases pain, inflammation • Prevents protective vasodilation, allows platelet clumping, which can lead to myocardial infarction and cerebrovascular accident • Myriad of skin reactions, including Stevens–Johnson syndrome