Acetylsalicylic acid (ASA)

Acetylsalicylic acid (ASA), often marketed as aspirin, is a medication used to relieve pain, fever, or inflammation. Specific inflammatory conditions for which aspirin is used include Kawasaki disease, pericarditis, and rheumatic fever. Aspirin given shortly after a heart attack reduces the risk of death. Aspirin is also used long-term to prevent further heart attacks, ischemic strokes, and blood clots in people at high risk. It may also reduce the risk of certain cancers, especially colorectal cancer. It typically takes effect within 30 minutes for pain or fever. Aspirin is a nonsteroidal anti-inflammatory drug (NSAID) and works similarly to other NSAIDs but also suppresses normal platelet function.

Pharmacodynamics

Acetylsalicylic acid (ASA) blocks prostaglandin synthesis. It is non-selective for the enzymes COX-1 and COX-2, and inhibition of these enzymes results in inhibition of platelet aggregation for approximately 7-10 days (average platelet lifespan). The acetyl group of acetylsalicylic acid binds to a serine residue of the enzyme cyclooxygenase-1 (COX-1), resulting in irreversible inhibition. This prevents the production of the prostaglandins that cause pain. This process also stops the conversion of arachidonic acid to thromboxane A2 (TXA2), which is a potent trigger for platelet aggregation. Platelet aggregation can lead to clots and harmful venous and arterial thromboembolism, resulting in conditions such as pulmonary embolism and stroke.

Pharmacokinetics

Absorption is generally rapid and complete following oral administration, but may vary widely depending on route of administration. 50% to 90% of a normal therapeutic concentration of salicylate (a major metabolite of acetylsalicylic acid) binds to plasma proteins, particularly albumin. Acetylsalicylic acid is hydrolyzed to salicylic acid in plasma and then further metabolized in the liver. Excretion of salicylates (metabolites of ASA) is mainly by the kidney.

Drug Interactions

Acetylsalicylic acid may interact with other drugs. Aspirin is known to displace a number of drugs from protein binding sites in the blood, including the antidiabetic drugs tolbutamide and chlorpropamide, warfarin, methotrexate, phenytoin, probenecid, valproic acid (as well as beta-oxidation, an important part of valproate metabolism), and other NSAIDs. This increases the plasma concentration of the aforementioned drugs and thus may lead to adverse side effects.

Corticosteroids may decrease the concentration of aspirin. Ibuprofen may abolish the antiplatelet effect of aspirin, which is used for cardioprotection and stroke prevention.

The pharmacologic activity of spironolactone may be decreased by aspirin ingestion, and it is known to compete with penicillin G for renal tubular secretion. Aspirin may also inhibit the absorption of vitamin C.

Side effects

Common adverse effects often involve the gastrointestinal tract.

More serious side effects include stomach ulcers, stomach bleeding, and exacerbation of asthma. The risk of bleeding is greater in people who are older, drink alcohol, take other NSAIDs, or take other blood thinners. Use of acetylsalicylic acid is not recommended during the last trimester of pregnancy. High doses may cause ringing in the ears.

Toxicological Data

_LD50 (rat, oral): 200 ^mg-kg-1