Aspirin

Summary

Aspirin is a non-steroidal anti-inflammatory drug that irreversibly inhibits the COX or cyclooxygenase enzymes. Low doses of aspirin target COX1 preferentially, while high doses of aspirin target both COX1 and COX2. COX enzymes typically produce prostaglandins and thromboxanes, so aspirin works to inhibit production of these inflammatory derivatives. Aspirin is clinically used as an analgesic, anti-inflammatory, and antipyretic agent. Importantly, aspirin is used as an antiplatelet agent, reducing formation of blood clots that lead to complications like myocardial infarction or stroke. Aspirin is also often given with niacin to reduce the side effect of cutaneous flushing.  Finally, aspirin helps reduce the risk of colon cancer by suppressing the growth of adenomatous polyps. A common side effect of aspirin use is the development of GI ulcers. Acute overdose leads to findings of tinnitus and metabolic acidosis. Importantly, aspirin should be avoided in children with febrile illnesses due to the risk of causing Reye’s syndrome, or aspirin-mediated liver failure.

Key Points

• Aspirin
  • Also known as acetylsalicylic acid (salicylate)
    • Converted to salicylic acid in the body
  • Mechanism
    • NSAID that irreversibly inhibits cyclooxygenase (COX) enzymes
      • Inhibition occurs by covalent acetylation
      • At low doses, mainly targets COX-1
        • Inhibits synthesis of prostaglandins, and thromboxanes
          • especially TXA2 by platelets, which mediates platelet aggregation
      • At higher doses, targets both COX-1 and COX-2
        • Inhibits synthesis of prostaglandins, leukotrienes, and other inflammatory arachidonic acid derivatives
  • Indications and Clinical Use
    • At low doses (<300 mg/day)
      • anti-platelet aggregation
        • Due to inhibition of thromboxane synthesis by platelets
        • Irreversible effects last until new platelets are produced (3-7 days)
      • Useful in prevention of cardiovascular events (e.g. MI, stroke)
      • Increased bleeding time (primary hemostasis)
        • No effect on PT, PTT (secondary hemostasis not changed)
    • At higher doses (>300 mg/day)
      • Antipyretic and anti-inflammatory agent
      • analgesia
    • Reduces colon cancer risk by inhibiting development of adenomatous polyps
      • COX-2 products are associated with adenomatous polyp growth
    • Reduces cutaneous flushing with niacin use
      • Due to inhibition of COX-1 mediated prostaglandin production
  • Adverse Effects
    • Acute Overdose
      • Tinnitus
      • Early hyperventilation (respiratory alkalosis)
      • Late metabolic acidosis
        • Due to increased production of lactic acid secondary to uncoupling of oxidative phosphorylation
        • Not due to salicylic acid directly
        • Treat with sodium bicarbonate
      • Vertigo, fever, nausea/vomiting, diarrhea also seen
    • Gastric ulcers and bleeding
      • GI ulcers and bleeding are the most common side effect seen with aspirin use
      • Due to impairment of prostaglandin-mediated GI mucosal defense
      • May also cause pill-induced esophagitis
    • Reye syndrome (acute liver failure) may occur in young children
      • Seen in with febrile viral illness
    • Bleeding (obvious)
      • Due to inhibition of platelet aggregation
    • Acute renal failure may occur (rare)
      • Due to interstitial nephritis or renal vasoconstriction
    • Aspirin allergy (hypersensitivity) may be seen