1. Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Chapter 71 Cyclooxygenase Inhibitors: Nonsteroidal Anti-Inflammatory Drugs and Acetaminophen

2. Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.2 Cyclooxygenase Inhibitors  Uses  Suppress inflammation  Relieve pain  Reduce fever  Adverse effects  Gastric ulceration  Bleeding  Renal impairment

3. Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.3 Classification of Cyclooxygenase Inhibitors  Drugs with anti-inflammatory properties  NSAIDs (nonsteroidal anti-inflammatory drugs) Aspirin, celecoxib, ibuprofen, and naproxen Aspirin, celecoxib, ibuprofen, and naproxen  Drugs without anti-inflammatory properties  Acetaminophen

4. Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.4 First-Generation NSAIDs  Inhibit COX-1 and COX-2  Used to treat inflammatory disorders (rheumatoid arthritis, osteoarthritis, bursitis)  Alleviate mild to moderate pain  Suppress fever  Relieve dysmenorrhea  Suppress inflammation but have risk of serious harm

5. Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.5 Aspirin  Nonselective inhibitor of cyclooxygenase  Therapeutic uses  Analgesic, antipyretic, anti-inflammatory  Suppression of platelet aggregation Protects in thrombotic disorders Protects in thrombotic disorders  Dysmenorrhea  Cancer prevention  Prevention of Alzheimer’s disease

6. Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.6 Aspirin  Adverse effects  Gastrointestinal effects  Bleeding  Renal impairment  Salicylism  Reye’s syndrome  Pregnancy Anemia, postpartum hemorrhage, may prolong labor Anemia, postpartum hemorrhage, may prolong labor  Hypersensitivity reaction

7. Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.7 Aspirin  Drug interactions  Anticoagulants: warfarin and heparin  Glucocorticoids  Alcohol  Ibuprofen  ACE inhibitors and ARBs  Acute poisonings

8. Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.8 Nonaspirin First-Generation NSAIDs  Aspirin-like drugs with fewer GI, renal, and hemorrhagic effects than aspirin  20+ nonaspirin NSAIDs available (all similar, but for unknown reasons, patients tend to do better on one drug or another)  Inhibit COX-1 and COX-2: inhibition is reversible (unlike with aspirin)  Principal indications: rheumatoid arthritis and osteoarthritis  Do not protect against myocardial infarction (MI) and stroke

9. Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.9 First-Generation NSAIDs  Ibuprofen (Advil, Motrin)  Fenoprofen  Flurbiprofen  Ketoprofen  Naproxen  Naproxen plus lansoprazole  Oxaprozin

10. Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.10 First-Generation NSAIDs  Diclofenac  Diclofenac plus misoprostol  Diflunisal  Etodolac  Indomethacin  Ketorolac  Mefenamic acid  Meclofenamate

11. Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.11 First-Generation NSAIDs  Nabumetone  Piroxicam  Sulindac  Tolmetin  Meloxicam

12. Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.12 Second-Generation NSAIDs  Just as effective as traditional NSAIDs in suppressing inflammation and pain  Somewhat lower risk for GI side effects  Can impair renal function and cause hypertension and edema  Increase risks for MI and stroke  In 2005, two coxibs withdrawn from use: rofecoxib (Vioxx) and valdecoxib (Bextra)  Use of celecoxib has sharply declined

13. Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.13 Celecoxib (Celebrex)  Second-generation COX-2 inhibitor—fewer adverse effects than first-generation drugs  Because of cardiovascular risks, last-choice drug for long-term management of pain  Uses  Osteoarthritis  Rheumatoid arthritis  Acute pain  Dysmenorrhea  Familial adenomatous polyposis

14. Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.14 Celecoxib (Celebrex)  Adverse effects  Dyspepsia  Abdominal pain  Renal toxicity  Sulfonamide allergy  Cardiovascular impact (stroke, MI, and other serious events)  Use in pregnancy

15. Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.15 Celecoxib (Celebrex)  Drug interactions  Warfarin  May decrease diuretic effect of furosemide  May decrease antihypertensive effect of ACE inhibitors  May increase levels of lithium  Levels of celecoxib may be increased by fluconazole

16. Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.16 Acetaminophen (Tylenol)  Therapeutic uses  Analgesic, antipyretic  Does not have any anti-inflammatory or antirheumatic actions  Not associated with Reye’s syndrome  Action  Inhibits prostaglandin synthesis in central nervous system

17. Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.17 Acetaminophen (Tylenol)  Adverse effects  Very few at normal doses  Hepatotoxicity With overdose or in patients with liver failure With overdose or in patients with liver failure  Overdose: hepatic necrosis Signs and symptoms of hepatic failure, coma, death Signs and symptoms of hepatic failure, coma, death Early symptoms: nausea and vomiting, diarrhea, sweating, abdominal pain Early symptoms: nausea and vomiting, diarrhea, sweating, abdominal pain Treatment for overdose: acetylcysteine (Mucomyst) Treatment for overdose: acetylcysteine (Mucomyst)

18. Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.18 Acetaminophen (Tylenol)  Drug interactions  Alcohol  Warfarin

19. Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.19 AHA Statement on COX Inhibitors  Most COX inhibitors, especially COX-2 inhibitors, increase the risk for MI and stroke  American Heart Association (AHA) recommends a stepped-care approach AHA = American Heart Association.