Singapore Drugs Database

Indication

For use in the temporary relief of various forms of pain, inflammation associated with various conditions (including rheumatoid arthritis, juvenile rheumatoid arthritis, systemic lupus erythematosus, osteoarthritis, and ankylosing spondylitis), and is also used to reduce the risk of death and/or nonfatal myocardial infarction in patients with a previous infarction or unstable angina pectoris.

Mechanism of Action

The analgesic, antipyretic, and anti-inflammatory effects of acetylsalicylic acid are due to actions by both the acetyl and the salicylate portions of the intact molecule as well as by the active salicylate metabolite. Acetylsalicylic acid directly and irreversibly inhibits the activity of both types of cyclooxygenase (COX-1 and COX-2) to decrease the formation of precursors of prostaglandins and thromboxanes from arachidonic acid. This makes acetylsalicylic acid different from other NSAIDS (such as diclofenac and ibuprofen) which are reversible inhibitors. Salicylate may competitively inhibit prostaglandin formation. Acetylsalicylic acid's antirheumatic (nonsteroidal anti-inflammatory) actions are a result of its analgesic and anti-inflammatory mechanisms; the therapeutic effects are not due to pituitary-adrenal stimulation. The platelet aggregation-inhibiting effect of acetylsalicylic acid specifically involves the compound's ability to act as an acetyl donor to cyclooxygenase; the nonacetylated salicylates have no clinically significant effect on platelet aggregation. Irreversible acetylation renders cyclooxygenase inactive, thereby preventing the formation of the aggregating agent thromboxane A2 in platelets. Since platelets lack the ability to synthesize new proteins, the effects persist for the life of the exposed platelets (7-10 days). Acetylsalicylic acid may also inhibit production of the platelet aggregation inhibitor, prostacyclin (prostaglandin I2), by blood vessel endothelial cells; however, inhibition prostacyclin production is not permanent as endothelial cells can produce more cyclooxygenase to replace the non-functional enzyme.

Pharmacokinetics

Absorption

Absorption is generally rapid and complete following oral administration but may vary according to specific salicylate used, dosage form, and other factors such as tablet dissolution rate and gastric or intraluminal pH.

Distribution

Metabolism

Acetylsalicylic acid is rapidly hydrolyzed primarily in the liver to salicylic acid, which is conjugated with glycine (forming salicyluric acid) and glucuronic acid and excreted largely in the urine.

Elimination

Toxicity

Oral, mouse: LD₅₀ = 250 mg/kg; Oral, rabbit: LD₅₀ = 1010 mg/kg; Oral, rat: LD₅₀ = 200 mg/kg. Effects of overdose include: tinnitus, abdominal pain, hypokalemia, hypoglycemia, pyrexia, hyperventilation, dysrhythmia, hypotension, hallucination, renal failure, confusion, seizure, coma, and death.

Active Ingredient/Synonyms

2-Acetoxybenzenecarboxylic acid | 2-Acetoxybenzoic acid | Acetylsalicylate | Acetylsalicylsäure | acide 2-(acétyloxy)benzoïque | acide acétylsalicylique | ácido acetilsalicílico | Acidum acetylsalicylicum | ASA | Aspirin | Azetylsalizylsäure | o-acetoxybenzoic acid | O-acetylsalicylic acid | o-carboxyphenyl acetate | Polopiryna | salicylic acid acetate | Acetylsalicylic acid |