Analgesic

Aspirin

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Aspirin, Acetylsalicylic acid, ASA, Durlaza

  • Indications
  1. Prevention of coronary and cerebrovascular events
  2. Analgesia in rheumatic conditions
  • 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
  • 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
  • Mechanism
  • NSAID related effects
  1. Antiinflammatory effect
    1. Inhibits prostaglandin biosynthesis
  2. Analgesic effect
    1. Relieves pain of mild to moderate intensity
  3. Antipyretic (Lowers Temperature)
  • Mechanism
  • Platelet Effects
  1. Inhibits Thromboxane synthesis
  2. Inhibits platelet aggregation
  3. Aspirin poisons the platelets for its remaining life
    1. New platelets are generated at a rate of 10% per day (25,000/day for a patient with a 250,000 Platelet Count)
    2. By 2 days off Aspirin, in this example, a patient will have 50,000 normal platelets (enough to counter bleeding)
    3. By 7 days off Aspirin, in this example, a patient will have 70% or 175,000 normal platelets (typical level required for elective surgery)
    4. By 10 days off Aspirin, in this example, a patient will have 100% or 250,000 normal platelets (level required by some clinicians for major surgery)
  • Dosing
  1. Use lowest appropriate dose (reduces adverse effects)
  2. Anticoagulation (Anti-Platelet action)
    1. General
      1. Do not exceed 160 mg daily 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)
        1. Prior recommendations: 325 mg orally daily
        2. New (2012) recommendations: 81 mg orally daily
          1. Similar efficacy in coronary disease prevention as the 325 mg dose
          2. Half the risk of gastrointestinal Hemorrhage as the 325 mg dose
        3. References
          1. Eikelboom (2012) Chest 141(2 Suppl):e89S-119S [PubMed]
    3. Cerebrovascular Accident
      1. Prevention in known vascular disease: 160-325 mg daily
      2. OConnor (2001) Am J Cardiol 88:541-6 [PubMed]
  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
  • Preparations
  • Extended Release Aspirin
  1. Durlaza ( Extended-release Aspirin)
    1. No evidence that extended release Aspirin ($6/pill) has advantages over Aspirin 81 mg ($0.01/pill)
    2. (2015) Presc Lett 22(12): 71
  • Drug Interactions
  1. Ibuprofen inactivates Aspirin Anticoagulation effect
    1. Competes for same receptors
    2. Naprosyn and Indocin do not do this
    3. Avoid NSAIDS in patients on prophylactic Aspirin for cardiovascular indications
  • Effects
  1. Non-platelet related activity (4 hour duration)
    1. Analgesic effect for mild to moderate pain at low dose
    2. Antiinflammatory effect at high dose
    3. Antipyretic effect
  2. Inhibition of platelet aggregation
    1. Irreversible platelet inhibition after single dose
    2. Effect lasts for the lifetime of platelet (8-10 days)
  • Advantages
  1. Safer and lower cost than many NSAIDs
  2. Aspirin is an underused medication
  • 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 [PubMed]
  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
  • Management
  • Reversal
  1. Platelet Transfusion 1 unit (6 pack)
  2. Consider Desmopressin (DDAVP) 0.3 mcg/kg (expert opinion)
  3. Consider Recombinant activated Clotting Factor VII (rFVIIa) 30-90 mcg/kg (expert opinion)
  • 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 [PubMed]