Download Cyclooxygenase Inhibitors

Anti-inflammatory Medications
Elsevier Inc. items and derived items © 2010 by Saunders, an imprint of Elsevier Inc.
Cyclooxygenase Inhibitors:
Nonsteroidal Anti-inflammatory Drugs
& Acetaminophen
Elsevier Inc. items and derived items © 2010 by Saunders, an imprint of Elsevier Inc.
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Cyclooxygenase Inhibitors

Uses
• Suppress inflammation
• Relieve pain
• Reduce fever

Adverse effects
• Gastric ulceration
• Bleeding
• Renal impairment
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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
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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
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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
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Aspirin

Adverse effects
•
•
•
•
•
•
Gastrointestinal effects
Bleeding
Renal impairment
Salicylism
Reye’s syndrome
Pregnancy
○ Anemia, postpartum hemorrhage, may
prolong labor
• Hypersensitivity reaction
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Aspirin

Drug interactions
•
•
•
•
•

Anticoagulants: warfarin and heparin
Glucocorticoids
Alcohol
Ibuprofen
ACE inhibitors and ARBS
Acute poisonings
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Nonaspirin First-Generation NSAIDs
Aspirin-like drug 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 MI and stroke
 See Table 70-5

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First-Generation NSAIDs







Ibuprofen (Advil, Motrin)*
Fenoprofen
Flurbiprofen
Ketoprofen
Naproxen*
Naproxen plus lansoprazole
Oxaprozin
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First-Generation NSAIDs




Diclofenac (Arthrotec)*
Diclofenac plus misoprostol
Indomethacin
Ketorolac (Toradol)*
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First-Generation NSAIDs





Nabumetone
Piroxicam
Sulindac
Tolmetin
Meloxicam
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Second-Generation NSAIDs
Just as effective as traditional NSAIDs
at suppressing inflammation and pain
 Somewhat lower risk for GI side effects
 Can impair renal function and cause
hypertension and edema
 Increase the risk for MI and stroke

• 2005, two coxibs withdrawn from use:
rofecoxib (Vioxx) and valdecoxib (Bextra)
• Use of celecoxib has sharply declined
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Celecoxib (Celebrex)
Second-generation COX-2 inhibitor—fewer
adverse effects than first-generation drugs
 Because of cardiovascular risks, lastchoice drug for long-term management of
pain
 Uses

•
•
•
•
•
Osteoarthritis
Rheumatoid arthritis
Acute pain
Dysmenorrhea
Familial adenomatous polyposis
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Celecoxib (Celebrex)

Adverse effects
•
•
•
•
•
Dyspepsia
Abdominal pain
Renal toxicity
Sulfonamide allergy
Cardiovascular impact (stroke, MI, and other
serious events)
• Use in pregnancy
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NSAID –adverse effects
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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
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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
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Metabolism of acetaminophen
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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
○ S/S of hepatic failure, coma, death
○ Early symptoms: N/V, diarrhea, sweating,
abdominal pain
○ Treatment for overdose: acetylcysteine
(Mucomyst)
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Acetaminophen (Tylenol)

Drug interactions
• Alcohol
• Warfarin
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Questions
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