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Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Chapter 71 Cyclooxygenase Inhibitors: Nonsteroidal Anti-Inflammatory Drugs and Acetaminophen
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
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
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
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
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
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
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
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
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
Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.11 First-Generation NSAIDs Nabumetone Piroxicam Sulindac Tolmetin Meloxicam
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
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
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
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
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
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)
Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.18 Acetaminophen (Tylenol) Drug interactions Alcohol Warfarin
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.
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