II. Indications

  1. Prevention of coronary and cerebrovascular events
  2. Analgesia in rheumatic conditions

III. 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

IV. 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

V. 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)

VI. 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)

VII. 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

VIII. 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

IX. 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

X. 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)

XI. Advantages

  1. Safer and lower cost than many NSAIDs
  2. Aspirin is an underused medication

XII. 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

XIII. 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)

XIV. 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]

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Cost: Medications

aspirin (on 5/17/2017 at Medicaid.Gov Survey of pharmacy drug pricing)
ASPIRIN 325 MG COATED TABLET Generic OTC $0.01 each
ASPIRIN 325 MG TABLET Generic OTC $0.01 each
ASPIRIN 81 MG CHEW TABLET Generic OTC $0.03 each
ASPIRIN 81 MG CHEWABLE TABLET Generic OTC $0.03 each
ASPIRIN 81 MG TABLET CHEW Generic OTC $0.03 each
ASPIRIN EC 325 MG TABLET Generic OTC $0.01 each
ASPIRIN EC 81 MG TABLET Generic OTC $0.01 each
ASPIRIN-DIPYRIDAM ER 25-200 MG Generic $4.03 each
asa (on 5/31/2017 at Medicaid.Gov Survey of pharmacy drug pricing)
ASA-BUTALB-CAFF-COD #3 CAPSULE Generic $1.77 each
ASACOL HD DR 800 MG TABLET Generic $5.46 each

Ontology: Aspirin (C0004057)

Definition (NCI) An orally administered non-steroidal antiinflammatory agent. Acetylsalicylic acid binds to and acetylates serine residues in cyclooxygenases, resulting in decreased synthesis of prostaglandin, platelet aggregation, and inflammation. This agent exhibits analgesic, antipyretic, and anticoagulant properties.
Definition (NCI_NCI-GLOSS) A drug that reduces pain, fever, inflammation, and blood clotting. Aspirin belongs to the family of drugs called nonsteroidal anti-inflammatory agents. It is also being studied in cancer prevention.
Definition (MSH) The prototypical analgesic used in the treatment of mild to moderate pain. It has anti-inflammatory and antipyretic properties and acts as an inhibitor of cyclooxygenase which results in the inhibition of the biosynthesis of prostaglandins. Aspirin also inhibits platelet aggregation and is used in the prevention of arterial and venous thrombosis. (From Martindale, The Extra Pharmacopoeia, 30th ed, p5)
Definition (CSP) prototypical analgesic used in the treatment of mild to moderate pain; has antiinflammatory and antipyretic properties and acts as an inhibitor of cyclooxygenase which results in the inhibition of the biosynthesis of prostaglandins; aspirin also inhibits platelet aggregation and is used in the prevention of arterial and venous thrombosis.
Definition (PDQ) An orally administered non-steroidal antiinflammatory agent. Acetylsalicylic acid binds to and acetylates serine residues in cyclooxygenases, resulting in decreased synthesis of prostaglandin, platelet aggregation, and inflammation. This agent exhibits analgesic, antipyretic, and anticoagulant properties. Check for "http://www.cancer.gov/Search/ClinicalTrialsLink.aspx?id=39152&idtype=1" active clinical trials or "http://www.cancer.gov/Search/ClinicalTrialsLink.aspx?id=39152&idtype=1&closed=1" closed clinical trials using this agent. ("http://nciterms.nci.nih.gov:80/NCIBrowser/ConceptReport.jsp?dictionary=NCI_Thesaurus&code=C287" NCI Thesaurus)
Concepts Pharmacologic Substance (T121) , Organic Chemical (T109)
MSH D001241
SnomedCT 322209007, 329524000, 319770009, 363583001, 391788009, 387458008, 7947003
English Acetylsalicylic Acid, Acid, Acetylsalicylic, Aspirin, 2-(Acetyloxy)benzoic Acid, Benzoic acid, 2-(acetyloxy)-, Aspirin [CNS], Aspirin [antiplatelet], aspirin, ASPIRIN, acetylsalicyclic acid, Aspirin [central nervous system use], Aspirin [musculoskeletal use], aspirin (medication), Antiplatelet aspirin, Aspirin [Chemical/Ingredient], aspirin antiplatelet, antiplatelet aspirin, aspirin products, aspirins, aspirin chemicals, acetylsalicylic acid, Aspirin [central nervous system use] (product), Aspirin [musculoskeletal use] (product), Aspirin product, Aspirin - chemical, Antiplatelet aspirin (product), Aspirin - chemical (substance), Aspirin product (substance), Acetylsalicylic acid - chemical, Acetylsalicylic acid, Aspirin (product), Aspirin (substance), Antiplatelet aspirin (substance), Aspirin [central nervous system use] (substance), Aspirin [musculoskeletal use] (substance), ASA
Swedish Acetylsalicylsyra
Spanish aspirina como tratamiento antiplaquetario (producto), aspirina (antiplaquetario), aspirina como antiplaquetario, aspirina [uso musculoesquelético], aspirina [uso musculoesquelético] (producto), producto con aspirina para tratamiento antiagregante, aspirina [indicada para el sistema nervioso central] (producto), aspirina [indicada para el sistema nervioso central], producto con aspirina para tratamiento antiagregante (producto), AAS, aspirina (sustancia), aspirina como tratamiento antiplaquetario, aspirina, ácido acetilsalicílico (producto), ácido acetilsalicílico (sustancia), ácido acetilsalicílico, Aspirina, Ácido Acetilsalicílico
Czech kyselina acetylsalicylová, Aspirin
Finnish Asetyylisalisyylihappo
Italian Acido 2-(acetilossi)benzoico, Acido acetilsalicilico, Aspirina
Russian ATSETILSALITSILOVAIA KISLOTA, ASPIRIN, АСПИРИН, АЦЕТИЛСАЛИЦИЛОВАЯ КИСЛОТА
Japanese アスピリン, アセチルサリチル酸
Croatian ASPIRIN
Polish ASA, Kwas acetylosalicylowy, Aspiryna
Norwegian Acetylsalisylsyre, Aspirin
French Acide acétylsalicylique, Aspirine
German ASS, Aspirin, Acetylsalicylsäure, Azetylsalizylsäure
Portuguese Ácido Acetilsalicílico, Aspirina