Transcript Chapter 16 Cholinesterase Inhibitors

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
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Gastric ulceration
Bleeding
Renal impairment
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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
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Acetaminophen
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First-Generation NSAIDs (aspirin,
-profen drugs, naproxyn)
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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
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Aspirin
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Nonselective inhibitor of cyclooxygenase
Irreversible inhibitor of cyclooxygenase
(effects last 7 days)
Therapeutic uses
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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
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Aspirin
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Adverse effects
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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)
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Hypersensitivity reaction- can be very serious,
treat with epinephrine
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Aspirin
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Drug interactions
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Anticoagulants: warfarin and heparin
Glucocorticoids- gastritis
Alcohol- gastritis, bleeding
Ibuprofen –
ACE inhibitors and ARBs- renal impairment
Acute poisonings
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Nonaspirin First-Generation NSAIDs
(-profens, naproxyn, ketorolac)
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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, also preferred over aspirin for
dysmenorrhea
Do not protect against myocardial infarction (MI) and
stroke
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First-Generation NSAIDs
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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
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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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Second-Generation NSAIDs
(celecoxib)
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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
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In 2005, two coxibs withdrawn from use:
rofecoxib (Vioxx) and valdecoxib (Bextra)
 Use of celecoxib has sharply declined
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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
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Osteoarthritis
Rheumatoid arthritis
Acute pain
 Dysmenorrhea
 Familial adenomatous polyposis
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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
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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
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Acetaminophen (Tylenol)
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Therapeutic uses
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Analgesic, antipyretic
Does not have any anti-inflammatory or
antirheumatic actions
Not associated with Reye’s syndrome
Action
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Inhibits prostaglandin synthesis in central nervous
system
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Acetaminophen (Tylenol)
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Adverse effects
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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)
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Acetaminophen (Tylenol)
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Drug interactions
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Alcohol
Warfarin
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AHA Statement on COX Inhibitors
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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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