Top Gene Interactions
- 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. 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.
- Uses/Sources: 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.
- Health Effects: Might increase the risk of gastrointestinal bleeding; large doses of salicylate, a metabolite of aspirin, have been proposed to cause tinnitus; Reye's syndrome, a severe illness characterized by acute encephalopathy and fatty liver, can occur when children or adolescents are given aspirin for a fever or other illnesses or infections. [Wikipedia]
- Symptoms: Effects of overdose include: tinnitus, abdominal pain, hypokalemia, hypoglycemia, pyrexia, hyperventilation, dysrhythmia, hypotension, hallucination, renal failure, confusion, seizure, coma, and death.
- Route of Exposure: 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.
- Carcinogenicity: No indication of carcinogenicity to humans (not listed by IARC).
- Toxicity: LD50: 250 mg/kg (Oral, Mouse) (A308) LD50: 1010 mg/kg (Oral, Rabbit) (A308) LD50: 200 mg/kg (Oral, Rat) (A308)
Mechanism of Action
|Target Name||Mechanism of Action||References|
Nuclear factor NF-kappa-B
NF-kappa-B inhibitor alpha
Ribosomal protein S6 kinase alpha-3
78 kDa glucose-regulated protein
Aldo-keto reductase family 1 member C1
Carbonic anhydrase 1
Inhibitor of nuclear factor kappa-B kinase subunit beta
Thyroid hormone receptor alpha
Carbonic anhydrase 2
Cellular tumor antigen p53
5'-AMP-activated protein kinase
Basic phospholipase A2 VRV-PL-VIIIa
Acidic phospholipase A2 3
Prostaglandin G/H synthase 2
Prostaglandin G/H synthase 1
|The analgesic, antipyretic, and anti-inflammatory effects of aspirin are due to actions by both the acetyl and the salicylate portions of the intact molecule as well as by the active salicylate metabolite. Aspirin directly and irreversibly inhibits the activity of both types of cyclo-oxygenase (COX-1 and COX-2) to decrease the formation of precursors of prostaglandins and thromboxanes from arachidonic acid. This makes aspirin different from other NSAIDS (such as diclofenac and ibuprofen) which are reversible inhibitors. Salicylate may competitively inhibit prostaglandin formation. Aspirin'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 aspirin specifically involves the compound's ability to act as an acetyl donor to the platelet membrane; the nonacetylated salicylates have no clinically significant effect on platelet aggregation. Aspirin affects platelet function by inhibiting the enzyme prostaglandin cyclooxygenase in platelets, thereby preventing the formation of the aggregating agent thromboxane A2. This action is irreversible; the effects persist for the life of the platelets exposed. Aspirin may also inhibit formation of the platelet aggregation inhibitor prostacyclin (prostaglandin I2) in blood vessels; however, this action is reversible.||