Aspirin

Aka: Aspirin, Acetylsalicylic acid, ASA, Durlaza

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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 (using an example patient with 250,000 Platelet Count)
    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, a patient will have 50,000 normal Platelets (enough to counter bleeding)
    3. By 7 days off Aspirin, a patient will have 70% or 175,000 normal Platelets (typical level required for elective surgery)
    4. By 10 days off Aspirin, a patient will have 100%normal Platelets (level required by some clinicians for major surgery)

VII. Dosing

  1. Use lowest appropriate dose (reduces adverse effects)
  2. Anti-Platelet action
    1. General
      1. Do not exceed 81 to 160 mg daily if on Coumadin
    2. Coronary Artery Disease
      1. Immediate Myocardial Infarction Management: 325 mg
      2. Primary coronary disease prevention: 81 mg orally daily
        1. As of 2018, Aspirin is no longer recommended for primary prevention in most patients
      3. Tertiary prevention (post-MI)
        1. Aspirin 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
        2. 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
  2. Vazalore (liquid-filled Aspirin capsule)
    1. Designed for delayed absorption to Small Intestine, postulated to reduce Gastrointestinal Bleeding
    2. No evidence that Vazalore reduces longterm Gastrointestinal Bleeding risk
    3. Expensive ($1 per capsule, compaired with $0.01/pill of standard Aspirin)
    4. (2021) Presc Lett 28(11): 62

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
    1. Aspirin is an underused medication
  2. Coronary disease prevention
    1. Falling out of favor in the primary prevention of lower risk patients without Myocardial Infarction or stroke
      1. Number Needed to Treat: 1 in 250 to prevent one first cardiovascular event (primary prevention)
      2. Aspirin is still an important mainstay of secondary prevention (known cardiovascular disease)
    2. Benefits may not outweigh the risks of GI Bleeding, Hemorrhagic CVA
      1. Number Needed to Harm: 1 in 200 to result in major bleeding
    3. References
      1. (2022) JAMA 327(16):1577-84 [PubMed]
  3. Other benefits
    1. May reduce Colorectal Cancer risk (NNT 77)

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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Related Studies

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
FPNotebook does not benefit financially from showing this medication data or their pharmacy links. This information is provided only to help medical providers and their patients see relative costs. Insurance plans negotiate lower medication prices with suppliers. Prices shown here are out of pocket, non-negotiated rates. See Needy Meds for financial assistance information.

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
Derived from the NIH UMLS (Unified Medical Language System)

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