Aspirin

1. Drug Name

• Generic Name: Aspirin

• Brand Names: Bayer, Ecotrin, Bufferin, St. Joseph, Aspro

2. Drug Classification

• Class: Nonsteroidal Anti-Inflammatory Drug (NSAID)

• Subclass: Salicylate

3. Mechanism of Action

• Aspirin irreversibly inhibits cyclooxygenase (COX-1 and COX-2) enzymes, preventing the conversion of arachidonic acid to prostaglandins and thromboxanes.

• COX-1 inhibition blocks thromboxane A2 production, which reduces platelet aggregation, conferring antiplatelet effects beneficial in cardiovascular disease.

• COX-2 inhibition reduces inflammation and pain, though COX-1 inhibition is primarily responsible for adverse gastrointestinal effects.

4. Pharmacokinetics

• Absorption: Rapidly absorbed from the gastrointestinal tract with peak plasma concentrations achieved within 1-2 hours.

• Distribution: Volume of distribution (Vd) is approximately 0.15-0.2 L/kg; around 80-90% is bound to plasma proteins.

• Metabolism: Primarily hydrolyzed in the liver to salicylic acid; conjugated to form inactive metabolites.

• Excretion: Half-life (t½) ranges from 2-3 hours (low doses) to approximately 15-30 hours at high doses, excreted primarily via the kidneys.

• Special Considerations: Half-life may increase significantly with higher doses due to saturable metabolism.

5. Indications

• Primary Indications:

  • Pain relief in mild to moderate pain (e.g., headache, muscle pain).

  • Anti-inflammatory agent in conditions like rheumatoid arthritis.

  • Antipyretic to reduce fever.

  • Cardiovascular protection for secondary prevention in individuals with a history of myocardial infarction (MI) or stroke.

• Off-Label Uses:

  • Prevention of colorectal cancer in high-risk populations.

• Specific Populations: Often indicated for adults, though its use in children is generally avoided due to the risk of Reye’s syndrome.

6. Dosage and Administration

• Adults:

  • Analgesic/Antipyretic: 325-650 mg every 4-6 hours, with a maximum daily dose of 4 grams.

  • Anti-inflammatory: 3-4 grams per day in divided doses.

  • Cardiovascular Prevention: Low-dose aspirin (75-325 mg once daily), with 81 mg being a common dose for daily prevention.

• Pediatric:

  • Generally avoided in children due to the risk of Reye’s syndrome, except in specific conditions like Kawasaki disease.

• Route: Oral or rectal formulations available.

• Dosing Adjustments: Use caution in renal or hepatic impairment; generally avoided in severe impairment.

• Maximum Safe Dose: Typically 4 grams per day for short-term analgesic use.

7. Contraindications

• Absolute Contraindications:

  • Known hypersensitivity to aspirin or other salicylates.

  • Active peptic ulcer disease.

  • Hemophilia or other bleeding disorders.

  • Children and adolescents with viral infections due to risk of Reye’s syndrome.

• Relative Contraindications:

  • Chronic renal or hepatic impairment.

  • Asthma or nasal polyps, as these may increase the risk of aspirin-induced asthma.

8. Warnings and Precautions

• Black Box Warnings: Not applicable.

• Special Warnings:

  • Increased risk of gastrointestinal bleeding and ulceration, especially in individuals with a history of GI disorders or concurrent NSAID use.

  • Use with caution in elderly patients, particularly with long-term use.

• Monitoring Parameters:

  • Regular monitoring of renal function and CBC in patients on long-term therapy, especially in those with risk factors for GI bleeding or renal impairment.

9. Adverse Effects

• Common Adverse Effects (≥10%): GI irritation, nausea, dyspepsia.

• Less Common but Clinically Significant: GI bleeding, tinnitus (especially at high doses), hypersensitivity reactions.

• Rare/Serious Adverse Reactions:

  • Severe GI bleeding and peptic ulcer perforation.

  • Reye’s syndrome in children.

  • Hemorrhagic stroke, especially in high doses.

10. Drug Interactions

• Major Drug Interactions:

  • Anticoagulants (e.g., warfarin): Increased bleeding risk.

  • NSAIDs: Increased risk of GI bleeding; NSAIDs may reduce aspirin’s cardioprotective effects.

  • Methotrexate: Increased methotrexate levels due to decreased renal clearance.

• Food-Drug Interactions: Food can delay absorption, though it may help reduce GI side effects.

• Interactions with Lab Tests: May prolong bleeding time.

11. Clinical Pharmacology

• Aspirin’s pharmacodynamics focus on COX inhibition, providing anti-inflammatory, analgesic, and antipyretic effects. Its unique irreversible COX-1 inhibition leads to prolonged antiplatelet effects, lasting for the life of the platelet (7-10 days).

12. Special Populations

• Pregnancy: Generally avoided, particularly in the third trimester due to risks of fetal ductus arteriosus closure and maternal bleeding.

• Lactation: Excreted in breast milk; use with caution in lactating mothers.

• Geriatrics: Higher risk of GI and renal complications; use at the lowest effective dose.

• Renal/Hepatic Dysfunction: Caution is advised in mild to moderate renal or hepatic impairment; generally avoided in severe cases.

13. Therapeutic Uses

• First-Line Therapy: Used for analgesic and antipyretic purposes in mild pain and fever; low-dose aspirin is a first-line therapy for cardiovascular prophylaxis.

• Second-Line or Adjunctive Therapy: Often used in combination with other antiplatelet agents in high-risk cardiovascular patients, with careful monitoring.

14. Monitoring and Follow-Up

• Recommended Lab Tests: Periodic CBC and renal function tests for patients on chronic therapy.

• Patient-Reported Symptom Checklists: Monitor for signs of GI bleeding (e.g., dark stools) and tinnitus.

• Monitoring of Therapeutic and Toxic Levels: Clinical monitoring for overdose symptoms such as tinnitus or metabolic acidosis.

15. Overdose Management

• Symptoms of Overdose: Tinnitus, vomiting, tachypnea, metabolic acidosis, confusion, seizures in severe cases.

• Treatment Protocols:

  • Activated charcoal if the patient presents within 1-2 hours of ingestion.

  • IV sodium bicarbonate to alkalinize urine and promote salicylate excretion.

  • Hemodialysis in cases of severe toxicity, particularly if serum salicylate levels are elevated or if the patient presents with severe symptoms.

16. Patient Counseling Information

• Counsel patients to take aspirin with food or a glass of water to minimize GI irritation.

• Inform about the risks of GI bleeding and signs to watch for, such as black or tarry stools.

• Advise patients to avoid other NSAIDs unless specifically instructed by a healthcare provider, to prevent increased bleeding risk.