Chapter 71
Cyclooxygenase Inhibitors:
Nonsteroidal Anti-Inflammatory
Drugs and Acetaminophen
Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
Cyclooxygenase Inhibitors
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Uses
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Suppress inflammation
Relieve pain
Reduce fever
Adverse effects



Gastric ulceration
Bleeding
Renal impairment
Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
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Classification of
Cyclooxygenase Inhibitors
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Drugs with anti-inflammatory properties
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
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.
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First-Generation NSAIDs
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Inhibit COX-1 and COX-2
Used to treat inflammatory disorders
(rheumatoid arthritis, osteoarthritis, bursitis)
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


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.
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Aspirin
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Nonselective inhibitor of cyclooxygenase
Therapeutic uses
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Analgesic, antipyretic, anti-inflammatory
Suppression of platelet aggregation
• Protects in thrombotic disorders
Dysmenorrhea
Cancer prevention
Prevention of Alzheimer’s disease
Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
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Aspirin
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Adverse effects
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Gastrointestinal effects
Bleeding
Renal impairment
Salicylism
Reye’s syndrome
Pregnancy
• Anemia, postpartum hemorrhage, may prolong labor
Hypersensitivity reaction
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Aspirin
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Drug interactions
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Anticoagulants: warfarin and heparin
Glucocorticoids
Alcohol
Ibuprofen
ACE inhibitors and ARBs
Acute poisonings
Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
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Nonaspirin First-Generation NSAIDs
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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.
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First-Generation NSAIDs
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Ibuprofen (Advil, Motrin)
Fenoprofen
Flurbiprofen
Ketoprofen
Naproxen
Naproxen plus lansoprazole
Oxaprozin
Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
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First-Generation NSAIDs
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Diclofenac
Diclofenac plus misoprostol
Diflunisal
Etodolac
Indomethacin
Ketorolac
Mefenamic acid
Meclofenamate
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First-Generation NSAIDs
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Nabumetone
Piroxicam
Sulindac
Tolmetin
Meloxicam
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Second-Generation NSAIDs
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
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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.
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Celecoxib (Celebrex)
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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.
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Celecoxib (Celebrex)
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Adverse effects
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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.
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Celecoxib (Celebrex)
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Drug interactions
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
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.
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Acetaminophen (Tylenol)
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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.
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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)
Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
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Acetaminophen (Tylenol)

Drug interactions


Alcohol
Warfarin
Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
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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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