Acetylsalicylic acid

1. See Also
   1. Salicylate
   2. Salicylate Toxicity
2. Indications
   1. Prevention of coronary and cerebrovascular events
   2. Analgesia in rheumatic conditions
3. Contraindications
   1. Children with viral illness (Varicella, Influenza)
      1. Risk of Reye's Syndrome (FDA Black Box Warning)
   2. Gout
   3. Hypersensitivity to Aspirin
   4. Active Peptic Ulcer Disease
4. History
   1. Willow bark contains Salicin (Salicylic acid)
      1. Used in folk medicine for mild pain and fever
   2. Acetylsalicylic acid is a derivative of salicylic acid
      1. Synthesized in 1853 by the Bayer brothers
5. Mechanism
   1. Antiinflammatory effect
      1. Inhibits prostaglandin biosynthesis
   2. Analgesic effect
      1. Relieves pain of mild to moderate intensity
   3. Antipyretic (Lowers temperature)
   4. Platelet Effects
      1. Inhibits Thromboxane synthesis
      2. Inhibits platelet aggregation
      3. Effects last 8 days (until new platelets)
6. Dosing
   1. Use lowest appropriate dose (reduces adverse effects)
   2. Anticoagulation (Anti-Platelet action)
      1. General
         1. Do not exceed 160 mg qd if on Coumadin
      2. Acute Myocardial Infarction
         1. Primary prevention: 81 mg PO qd
         2. Immediate Myocardial Infarction Management: 325 mg
         3. Tertiary prevention (post-MI): 325 mg PO qd
      3. Cerebrovascular Accident
         1. Prevention in known vascular disease: 160-325 mg qd
         2. O'Connor (2001) Am J Cardiol 88:541-6
   3. Antipyretic or Analgesic Dose
      1. Adult: 600 mg PO q4 hours
      2. Adult: 650-1000 mg PO q4-6 hours
   4. Antiinflammatory dose
      1. Adult: 4 grams maximum per day
7. Drug Interactions
   1. Ibuprofen inactivates Aspirin Anticoagulation effect
      1. Competes for same receptors
      2. Naprosyn and Indocin do not do this
8. Effects
   1. Analgesic effect for mild to moderate pain at low dose
   2. Antiinflammatory effect at high dose
   3. Antipyretic effect
   4. Inhibition of platelet aggregation
      1. Irreversible platelet inhibition after single dose
      2. Effect lasts for the lifetime of platelet (8-10 days)
9. Pharmacokinetics
   1. Duration: 4 hours
10. Advantages
    1. Safer and lower cost than many NSAIDs
    2. Aspirin is an underused medication
11. Adverse effects
    1. Gastrointestinal Effects
       1. Gastrointestinal intolerance
       2. Peptic Ulcer Disease (Erosive Gastritis)
          1. Aspirin higher risk for Peptic Ulcer Disease
          2. Other Salicylates have lower risk than most NSAIDs
       3. Gastrointestinal Bleeding
          1. Middle aged: 2-4 per 1000 on Aspirin 5 years
          2. Older patient: 4-12 per 1000 on Aspirin for 5 years
          3. Roderick (1993) Br J Clin Pharmacol 35:219-26
    2. Central Nervous System Effects: Salicylism
       1. Tinnitus
       2. Decreased hearing acuity
       3. Vertigo
    3. Central Respiratory effects
       1. Very high dose: Hyperpnea
       2. Lethal doses: Respiratory depression or apnea
    4. Miscellaneous Effects
       1. Serum Uric Acid changes
          1. Aspirin <2 g/day: increases serum Uric Acid
          2. Aspirin >4 g/day: lowers serum Uric Acid <2.5 mg/dl
       2. Asymptomatic hepatitis
       3. Exacerbation of renal insufficiency
       4. Hypersensitivity Reaction (Aspirin Allergy)
          1. Associated with Nasal Polyps and Asthma
12. References
    1. McCarty (1972) Arthritis and Allied Conditions
    2. Katzung (1989) Basic and Clinical Pharmacology
    3. (2000) Med Lett Drugs Ther 42(1085):73-8