Acetylsalicylic Acid (Aspirin)

General Information

  • Aspirin is the Most Commonly Used Drug in the World

Indications


Contraindications

  • Chronic Kidney Disease (CKD) (see Chronic Kidney Disease, [[Chronic Kidney Disease]])
    • Due to Risk of Worsening Chronic Kidney Disease
  • Chronic Liver Disease (see End-Stage Liver Disease, [[End-Stage Liver Disease]])
    • Due to Frequent Co-Existing Chronic Kidney Disease (and Risk of Hepatorenal Syndrome) (see Hepatorenal Syndrome, [[Hepatorenal Syndrome]])
    • Due to Risk of Gastrointestinal Hemorrhage (see Gastrointestinal Hemorrhage, [[Gastrointestinal Hemorrhage]])

Pharmacology

Metabolism

  • Hepatic: predominantly

Administration

  • PO: 81 mg or 325 mg qday

Dose Adjustment

  • Hepatic
  • Renal

Management of Aspirin Therapy for Minor Dental, Dermatologic, or Ophthalmologic Procedures

  • Recommendations (Chest Antithrombotic Therapy and Prevention of Thrombosis 2012 Guidelines) [MEDLINE]
    • xxx

3.4 Patients Undergoing a Minor Dental, Dermatologic, or Ophthalmologic Procedure
3.4. In patients who are receiving acetylsali- cylic acid (ASA) for the secondary prevention of cardiovascular disease and are having minor dental or dermatologic procedures or cataract surgery, we suggest continuing ASA around the time of the procedure instead of stopping ASA 7 to 10 days before the procedure (Grade 2C).

3.5. In patients at moderate to high risk for cardiovascular events who are receiving ASA therapy and require noncardiac surgery, we suggest continuing ASA around the time of sur- gery instead of stopping ASA 7 to 10 days before surgery (Grade 2C). In patients at low risk for cardiovascular events who are receiving ASA therapy, we suggest stopping ASA 7 to 10 days before surgery instead of continuation of ASA (Grade 2C).

3.6 Patients Undergoing Coronary Artery Bypass Graft Surgery
3.6. In patients who are receiving ASA and require coronary artery bypass graft (CABG) surgery, we suggest continuing ASA around the time of surgery instead of stopping ASA 7 to 10 days before surgery (Grade 2C). In patients who are receiving dual antiplatelet drug therapy and require CABG surgery, we suggest con- tinuing ASA around the time of surgery and stopping clopidogrel/prasugrel 5 days before surgery instead of continuing dual antiplatelet therapy around the time of surgery (Grade 2C).

3.7. In patients with a coronary stent who are receiving dual antiplatelet therapy and require surgery, we recommend deferring surgery for at least 6 weeks after placement of a bare-metal stent and for at least 6 months after placement of a drug-eluting stent instead of undertaking surgery within these time periods (Grade 1C). In patients who require surgery within 6 weeks of placement of a bare-metal stent or within 6 months of placement of a drug-eluting stent, we suggest continuing dual antiplatelet therapy around the time of surgery instead of stopping dual antiplatelet therapy 7 to 10 days before surgery (Grade 2C).

Remarks: Patients who are more concerned about avoiding the unknown, but potentially large increase in bleeding risk associated with the perioperative continuation of dual antiplatelet therapy than avoid- ing the risk for coronary stent thrombosis are unlikely to choose continuation of dual antiplatelet therapy.


Adverse Effects

Cardiovascular Adverse Effects

Pseudo-Sepsis Syndrome (see Hypotension, [[Hypotension]])

  • Epidemiology
    • Associated with chronic salicylate ingestion
  • Diagnosis: elevated salicylate level
  • Clinical
    • Acute Lung Injury-ARDS (see Acute Lung Injury-ARDS, [[Acute Lung Injury-ARDS]])
    • Fever (see Fever, [[Fever]])
    • Leukocytosis
    • Hypotension (see Hypotension, [[Hypotension]])
    • Multiple Organ Failure
  • Treatment: as for salicylate intoxication

Endocrinologic Adverse Effects

Drug-Induced Hyporeninemic Hypoaldosteronism (see Hypoaldosteronism, [[Hypoaldosteronism]])

  • Physiology
    • Class effect, common to all NSAID’s
    • Dose-dependent COX-inhibition -> decreased renal prostaglandin synthesis -> results in drug-induced hyporeninemic hypoaldosteronism
  • Clinical

Gastrointestinal Adverse Effects

Peptic Ulcer Disease (PUD) (see Peptic Ulcer Disease, [[Peptic Ulcer Disease]])

  • Physiology: class effect, common to all NSAID’s

Hematologic Adverse Effects

Pulmonary Adverse Effects

Aspirin-Intolerant Asthma (see Asthma, [[Asthma]])

  • Epidemiology
    • Class effect, common to all NSAID’s
    • Up to 5% of asthmatics are sensitive to aspirin
  • Physiology: unknown -> may involve COX inhibition resulting in decreased production of bronchodilator PGE2 and increased production of leukotrienes
    • Not dose-related -> can occur with even small doses of aspirin
  • Clinical
    • Samter’s Syndrome: aspirin sensitivity + asthma + nasal polyps
    • Commonly associated are rash and GI side effects
    • ASA may cause fatal bronchospasm

Drug-Induced Pulmonary Eosinophilia (see Drug-Induced Pulmonary Eosinophilia, [[Drug-Induced Pulmonary Eosinophilia]])

  • Associated Agents
    • Acetylsalicylic Acid (Aspirin) (see Acetylsalicylic Acid, [[Acetylsalicylic Acid]])
    • Diclofenac (Aclonac, Cataflam, Voltaren) (see Diclofenac, [[Diclofenac]])
    • Diflunisal (Dolobid)
    • Fenbufen
    • Fenoprofen (see Fenoprofen, [[Fenoprofen]]): case reports
    • Ibuprofen (Advil, Brufen, Motrin, Nurofen) (see Ibuprofen, [[Ibuprofen]]): case reports
    • Indomethacin (Indocin) (see Indomethacin, [[Indomethacin]])
    • Loxoprofen
    • Meloxicam (see Meloxicam, [[Meloxicam]])
    • Naproxen (Naprosyn, Aleve) (see Naproxen, [[Naproxen]]): appears to be more frequent with naproxen than other NSAID’s
    • Nimesulide
    • Phenylbutazone
    • Piroxicam (Feldene) (see Piroxicam, [[Piroxicam]])
    • Pranoprofen
    • Sulindac (Clinoril) (see Sulindac, [[Sulindac]]): case reports
    • Tenidap
    • Tiaprofenic Acid
    • Tolfenamic Acid
  • Diagnosis
    • Lung Biopsy: poorly defined granulomas with infiltrating eosinophils
  • Clinical
    • Cough
    • Dyspnea
    • Fever
    • Peripheral Eosinophilia
    • Pulmonary Infiltrates

Renal Adverse Effects

Acute Interstitial Nephritis (see Acute Interstitial Nephritis, [[Acute Interstitial Nephritis]])

  • Physiology: class effect, common to all NSAID’s

Acute Kidney Injury (AKI) (see Acute Kidney Injury, [[Acute Kidney Injury]])

  • xxxx

Hyperkalemia (see Hyperkalemia, [[Hyperkalemia]])

  • Mechanism: due to drug-induced hyporeninemic hypoaldosteronism

Increased Renal Sodium Reabsorption with Peripheral Edema

  • Risk Factors
  • Physiology: decreased PGE2 -> increased renal sodium reabsorption
    • Class Effect: common to all NSAID’s
    • Dose-Dependent Effect
  • Clinical: typically occurs during the first week of therapy

Type 4 Renal Tubular Acidosis (RTA) (see Type 4 Renal Tubular Acidosis, [[Type 4 Renal Tubular Acidosis]])

  • Physiology: due to NSAID-induced hyporeninemic hypoaldosteronism
  • Clinical

Other Adverse Effects

  • xxxx

Salicylate Intoxication


Aspirin Desensitization Therapy

  • Indications
    • xxxxx
  • Protocol
    • Time 0:
    • Time 30 min
    • Time 60 min:
    • Etc

References

  • Death following ingestion of five grains of acetylsalicylic acid. JAMA 1933; 101: 446
  • Transient pulmonary eosinophilia and asthma. A review of 20 cases occurring in 5,702 asthma sufferers. Am Rev Respir Dis. 1966 May;93(5):797-803 [MEDLINE]
  • Intolerance to aspirin: clinical studies and consideration of its pathogenesis. Ann Intern Med 1968; 68: 975-983
  • Salicylate-induced pulmonary edema: clinical features and prognosis. Ann Intern Med 1981; 95: 405-409
  • Adverse pulmonary responses to aspirin and acetaminophen in chronic chilhood asthma. Pediatrics 1983; 71: 313-318
  • Aspirin idiosyncrasy and tolerance. J Allergy Clin Immunol 1984; 73: 431-434
  • Aspirin intolerance and asthmal induction of a tolerance and long-term monitoring. Clin Allergy 1985; 15: 37-42
  • Adult respiratory distress syndrome induced by salicylate toxicity. Postgrad Med 1985; 78: 117-9, 123
  • Aspirin, paracetamol and non-steroidal anti-inflammatory drugs. A comparative review of side-effects. Med Toxicol 1987; 2: 338-366
  • Bronchial asthma, nasal polyps, and aspirin sensitivity: Samter’s syndrome. Clin Chest Med. 1988 Dec;9(4):567-76
  • [Loeffler syndrome in a child treated with aspirin][Article in Hebrew]. Harefuah. 1990 Mar 1;118(5):262-4 [MEDLINE]
  • Antipyretic effect of lumbricus spencer in acetylsalicylic acid-induced asthma – A pilot study. Arzneim Forsch 1996; 46: 172-174
  • Mechanism of aspirin-induced asthma. Allergy 1997; 52: 613-619
  • Recurrent ARDS in an 39-year-old woman with migraine headaches. Chest 1998; 114: 919-22
  • Hemoptysis during lung biopsy after aspirin. Am J Roentgenol 1998; 171: 261
  • Aspirin-induced asthma and Churg-Strauss-syndrome. Eur J Clin Invest 1998; 28 Suppl 1: A49
  • Hemoptysis during lung biopsy after aspirin. Am J Roentgenol 1998; 171: 261
  • Executive summary: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest. 2012 Feb;141(2 Suppl):7S-47S. doi: 10.1378/chest.1412S3 [MEDLINE]