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Chapter 71

Chapter 71. Cyclooxygenase Inhibitors: Nonsteroidal Anti-Inflammatory Drugs and Acetaminophen. Cyclooxygenase Inhibitors. Uses Suppress inflammation Relieve pain Reduce fever Adverse effects Gastric ulceration Bleeding Renal impairment. Classification of Cyclooxygenase Inhibitors.

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Chapter 71

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  1. Chapter 71 Cyclooxygenase Inhibitors:Nonsteroidal Anti-Inflammatory Drugs and Acetaminophen

  2. Cyclooxygenase Inhibitors • Uses • Suppress inflammation • Relieve pain • Reduce fever • Adverse effects • Gastric ulceration • Bleeding • Renal impairment

  3. Classification of Cyclooxygenase Inhibitors • Drugs with anti-inflammatory properties • NSAIDs (nonsteroidal anti-inflammatory drugs) • Aspirin, celecoxib, ibuprofen, and naproxen • Drugs without anti-inflammatory properties • Acetaminophen

  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. Aspirin • Nonselective inhibitor of cyclooxygenase • Therapeutic uses • Analgesic, antipyretic, anti-inflammatory • Suppression of platelet aggregation • Protects in thrombotic disorders • Dysmenorrhea • Cancer prevention • Prevention of Alzheimer’s disease

  6. Aspirin • Adverse effects • Gastrointestinal effects • Bleeding • Renal impairment • Salicylism • Reye’s syndrome • Pregnancy • Anemia, postpartum hemorrhage, may prolong labor • Hypersensitivity reaction

  7. Aspirin • Drug interactions • Anticoagulants: warfarin and heparin • Glucocorticoids • Alcohol • Ibuprofen • ACE inhibitors and ARBs • Acute poisonings

  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. First-Generation NSAIDs • Ibuprofen (Advil, Motrin) • Fenoprofen • Flurbiprofen • Ketoprofen • Naproxen • Naproxen plus lansoprazole • Oxaprozin

  10. First-Generation NSAIDs • Diclofenac • Diclofenac plus misoprostol • Diflunisal • Etodolac • Indomethacin • Ketorolac • Mefenamic acid • Meclofenamate

  11. First-Generation NSAIDs • Nabumetone • Piroxicam • Sulindac • Tolmetin • Meloxicam

  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. 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. Celecoxib (Celebrex) • Adverse effects • Dyspepsia • Abdominal pain • Renal toxicity • Sulfonamide allergy • Cardiovascular impact (stroke, MI, and other serious events) • Use in pregnancy

  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. 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. Acetaminophen (Tylenol) • Adverse effects • Very few at normal doses • Hepatotoxicity • With overdose or in patients with liver failure • Overdose:hepatic necrosis • Signs and symptoms of hepatic failure, coma, death • Early symptoms: nausea and vomiting, diarrhea, sweating, abdominal pain • Treatment for overdose: acetylcysteine (Mucomyst)

  18. Acetaminophen (Tylenol) • Drug interactions • Alcohol • Warfarin

  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.

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