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Transcript
Chapter 71 Cyclooxygenase Inhibitors: Nonsteroidal Anti-Inflammatory Drugs and Acetaminophen Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. 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. 2 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 Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. 3 First-Generation NSAIDs (aspirin, -profen drugs, naproxyn) 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. 4 Aspirin Nonselective inhibitor of cyclooxygenase Irreversible inhibitor of cyclooxygenase (effects last 7 days) Therapeutic uses Analgesic, antipyretic, anti-inflammatory Suppression of platelet aggregation (aspirin is unique for this benefit) • Protects in thrombotic disorders Dysmenorrhea Cancer prevention Prevention of Alzheimer’s disease Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. 5 Aspirin Adverse effects Gastrointestinal effects Bleeding Renal impairment (watch BUN/creatinine, urine output, increasing signs/symptoms of fluid overload esp. in older patients with risk factors) Salicylism Reye’s syndrome (avoid in children) Pregnancy • Anemia, postpartum hemorrhage, may prolong labor, also premature closure of ductus arterious in fetus) Hypersensitivity reaction- can be very serious, treat with epinephrine Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. 6 Aspirin Drug interactions Anticoagulants: warfarin and heparin Glucocorticoids- gastritis Alcohol- gastritis, bleeding Ibuprofen – ACE inhibitors and ARBs- renal impairment Acute poisonings Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. 7 Nonaspirin First-Generation NSAIDs (-profens, naproxyn, ketorolac) 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, also preferred over aspirin for dysmenorrhea Do not protect against myocardial infarction (MI) and stroke Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. 8 First-Generation NSAIDs Ibuprofen (Advil, Motrin) Fenoprofen Flurbiprofen Ketoprofen (powerful analgesic, often used post-op, for short-term management of moderate to severe pain, not to exceed 5 days) Naproxen Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. 9 First-Generation NSAIDs Diclofenac Diclofenac plus misoprostol Diflunisal Etodolac Indomethacin Ketorolac Mefenamic acid Meclofenamate Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. 10 Second-Generation NSAIDs (celecoxib) 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. 11 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. 12 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. 13 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. 14 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. 15 Acetaminophen (Tylenol) Adverse effects Very few at normal doses (has minimal effects at peripheral sites, acts on cyclooxygenase in the CNS) 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) Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. 16 Acetaminophen (Tylenol) Drug interactions Alcohol Warfarin Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. 17 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. Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. 18