CHAPTER © 2012 The McGraw-Hill Companies, Inc. All rights reserved. 20 Nonopioid Analgesics, Nonsteroidal Antiinflammatories, and Antigout Drugs

© 2012 The McGraw-Hill Companies, Inc. All rights reserved. Inflammation The inflammatory process is a normal response to injury. Inflammation is considered the first step in the process of healing. Inflammation can become exaggerated, which leads to further tissue damage. 20-2

© 2012 The McGraw-Hill Companies, Inc. All rights reserved. Inflammation 20-3

© 2012 The McGraw-Hill Companies, Inc. All rights reserved. Antiinflammatory Drug Action Steroidal antiinflammatory drugs decrease inflammation by inhibiting cyclooxygenase enzymes. (look at article on COX-1 and COX-2) Nonsteroidal antiinflammatory drugs decrease inflammation by inhibiting prostaglandin synthesis. 20-4

© 2012 The McGraw-Hill Companies, Inc. All rights reserved. Nonopioids 20-5 There are three groups within this class distinguished by their pharmacologic action: –Salicylates –Traditional NSAIDs –COX-2 selective inhibitors

© 2012 The McGraw-Hill Companies, Inc. All rights reserved. Salicylates 20-6 Aspirin and salicylic acid are the main salicylates: –Oldest and most frequently used nonopioid analgesics –Used as analgesics, antipyretics, and antiinflammatories –Discovered from Native Americans’ use of willow tree bark

© 2012 The McGraw-Hill Companies, Inc. All rights reserved. Salicylates 20-7 Salicylates produce analgesia and antipyresis by affecting the hypothalamic centers in the brain. Aspirin is a potent inhibitor of prostaglandin synthesis, which decreases inflammation. Salicylates block COX-1: –Protective environment in stomach is altered –Gastric ulcers can result

© 2012 The McGraw-Hill Companies, Inc. All rights reserved. Salicylates 20-8 Aspirin: –Helps reduce risk of reinfarction –Prevents heart disease Salicylate intoxication: –Nausea, vomiting, salicylism Aspirin should not be given to children with chickenpox or flu symptoms: –Reye’s syndrome

© 2012 The McGraw-Hill Companies, Inc. All rights reserved. Salicylates 20-9 Aspirin: –Used for mild to moderate pain, osteoarthritis, and rheumatoid arthritis –Reduces inflammation Aspirin safe for use in adults and children. –Available in a variety of formulations: Capsules Tablets Solutions Gums

© 2012 The McGraw-Hill Companies, Inc. All rights reserved. Salicylates 20-10

© 2012 The McGraw-Hill Companies, Inc. All rights reserved. Acetaminophen Acetaminophen is effective in treating headaches, fever, and minor musculoskeletal pain. –Inhibits prostaglandin synthetase –Considered an aspirin substitute –Does not have antiinflammatory properties –Not useful in the treatment of arthritis 20-11

© 2012 The McGraw-Hill Companies, Inc. All rights reserved. Acetaminophen Acetaminophen is available in a variety of formulations: –Suppository –Solution –Elixir –Suspension –Syrup It is available without a prescription Toxicity may develop from chronic use

© 2012 The McGraw-Hill Companies, Inc. All rights reserved. Acetaminophen Treatment for overdose includes: –Gastric aspiration and lavage –Maintenance of fluid balance –Activated charcoal –N-acetylcysteine Because acetaminophen is available in several OTC combination treatments, toxicity is a concern

© 2012 The McGraw-Hill Companies, Inc. All rights reserved. NSAIDs All NSAIDs interact with cyclooxygenases. Available primarily for oral administration. Older NSAIDs are nonselective. Newer NSAIDs are selective COX-2 inhibitors: –Reduce inflammation –Pain relief not superior to older NSAIDs –Lower incidence of ulcers and gastric bleeding 20-14

© 2012 The McGraw-Hill Companies, Inc. All rights reserved. NSAIDs All antiinflammatory drugs may produce: –Nausea, GI distress, and ulceration –Vertigo, vomiting, mental confusion, and headaches Overdose of NSAIDs is similar to salicylate overdose. –No specific antidote for NSAID poisoning NSAID use is discouraged in elderly patients

© 2012 The McGraw-Hill Companies, Inc. All rights reserved. NSAIDs Every OTC product with an NSAID should include a warning for severe stomach bleeding in people who: –Are aged 60 years or older –Have had stomach ulcers or bleeding problems –Take a blood thinning or steroid drug –Take other drugs containing prescription or nonprescription NSAIDs –Have three or more alcoholic drinks a day while using the product 20-16

© 2012 The McGraw-Hill Companies, Inc. All rights reserved. Gout Gout is an inflammatory disease caused by uric acid crystal formations in the joints and soft tissue. Some foods with high purine content precipitate gouty attacks. Inflammation of the joint is caused by phagocytes trying to remove the uric acid deposits

© 2012 The McGraw-Hill Companies, Inc. All rights reserved. Drugs Useful in Treating Gout Drugs that are useful in the treatment of gout either relieve the acute inflammatory response or reduce uric acid levels. Colchicine alters the phagocytes’ ability to attack the uric acid crystals. Colchicine causes nausea, vomiting, diarrhea, and hematuria

© 2012 The McGraw-Hill Companies, Inc. All rights reserved. Drugs Useful in Treating Gout Two major classes of drugs used in long-term prophylaxis of gout: –Hypouricemic agents Allopurinol Febuxostat –Uricosuric agents Probenecid 20-19

© 2012 The McGraw-Hill Companies, Inc. All rights reserved. Drugs Useful in Treating Gout 20-20

© 2012 The McGraw-Hill Companies, Inc. All rights reserved. Drug Interactions Antiinflammatory drugs and nonopioid analgesics undergo a variety of drug interactions due to displacement on the protein binding site. Aspirin may cancel the uricosuric effect of probenecid. Rifampin and acetaminophen given concurrently increase the risk of liver toxicity

© 2012 The McGraw-Hill Companies, Inc. All rights reserved. Preferred Therapy Aspirin: –Fever, headaches, inflammation including arthritis, prophylaxis of heart attack or stroke Ibuprofen: –Aches, pains, inflammation Acetaminophen: –Fever and headache, aspirin substitute Colchicine, allopurinol, and probenecid: –Gout 20-22