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. |
Pharmacodynamics |
Acetylsalicylic acid is an analgesic, antipyretic,
antirheumatic, and anti-inflammatory agent. Acetylsalicylic acid's mode
of action as an antiinflammatory and antirheumatic agent may be due to
inhibition of synthesis and release of prostaglandins. Acetylsalicylic
acid appears to produce analgesia by virtue of both a peripheral and CNS
effect. Peripherally, acetylsalicylic acid acts by inhibiting the
synthesis and release of prostaglandins. Acting centrally, it would
appear to produce analgesia at a hypothalamic site in the brain,
although the mode of action is not known. Acetylsalicylic acid also acts
on the hypothalamus to produce antipyresis; heat dissipation is
increased as a result of vasodilation and increased peripheral blood
flow. Acetylsalicylic acid's antipyretic activity may also be related to
inhibition of synthesis and release of prostaglandins. |
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. |
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. |
Volume of distribution |
Not Available |
Protein binding |
High (99.5%) to albumin. Decreases as plasma salicylate
concentration increases, with reduced plasma albumin concentration or
renal dysfunction, and during pregnancy. |
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. |
Route of elimination |
Not Available |
Half life |
The plasma half-life is approximately 15 minutes; that for
salicylate lengthens as the dose increases: doses of 300 to 650 mg have a
half-life of 3.1 to 3.2 hours; with doses of 1 gram, the half-life is
increased to 5 hours and with 2 grams it is increased to about 9 hours. |
Clearance |
Not Available |
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. |