Aspirin

History of the Drug

Salicylic acid, the compound form from which aspirin was first derived, was found in the bark of the willow tree by Edmund Stone in England in 1763. Charles F. Gerhardt synthesized the first derivative of salicylic acid in 1853 (see Figures 1 and 2), but it wasn’t until 1899 that aspirin, or acetylsalicylic acid, was first synthesized by Felix Hoffman, an employee of Bayer, and trademarked by Bayer (see Figures 3 and 4). ‘Aspirin’ is the Bayer-registered trademark for acetylsalicylic acid (Mann, 1991).

Usable form and trade names

Aspirin is the trade name of the drug acetylsalicylic acid, and aspirin is available in many dosage forms, from 60 to 650 milligrams. Aspirin comes in many forms: tablet, capsules, caplets, liquid and also in suppository form. The recommended daily dose of aspirin depends on the individual and the condition being treated: low daily doses of aspirin are, for example, recommended to prevent coronary disorders in the elderly, although higher doses would be recommended for younger individuals experiencing temporary pain.

Mode of Action

The mode of action of aspirin was unknown until quite recently. It is now, however, believed that aspirin blocks the production of prostaglandins, the molecules responsible for producing pain, by inhibiting the activity of both types of cyclo-oxygenase (COX-1 and COX-2), through competitive inhibition, thus decreasing the formation of pre-cursors of prostaglandins (see Figure 5) (Catella-Lawson et al., 2001). It is known that this competitive inhibition occurs by blocking a serine residue (see Figure 6) (Catella-Lawson et al., 2001). A similar pathway is followed to block the formation of thromboxanes (a family of prostaglandins), the molecules responsible for platelet aggregation and vasoconstriction, thus aiding with blood thinning and increased blood flow around the body (Catella-Lawson et al., 2001). It is also hypothesized that aspirin can prevent the formation of cells that cause inflammation through its analgesic and anti-inflammatory mechanisms of action, which are still little understood (see Figures 7) (Catella-Lawson et al., 2001).

Pharmacology

The pharmacology of aspirin is complex and, until recently, was unknown. It is, however, now known that aspirin’s analgesic action occurs because aspirin is a competitive inhibitor of the cyclooxygenases, and therefore of prostaglandin synthesis (Catella-Lawson et al., 2001), preventing the formation of prostoglandins, the molecules responsible for producing pain. In addition, aspirin also has an anti-inflammatory action, as it acts to form lipoxins (see Figure 8) which have anti-inflammatory properties and which induce synthesis of anti-inflammatory mediators, known as resolvins (Rvs) and protectins (PDs) (Koester, 1993). It is also thought that, in addition to competitively inhibiting cyclooxygenases and producing lipoxins, aspirin also impinges upon the formation of 12-HETE, a chemotactic agent, derived from leukotriene, providing analgesic action, and influencing the migration of neutrophils and monocytes, aiding in inflammation reduction (Koester, 1993). In addition, aspirin inhibits the formation of thromboxanes (vasoconstrictors) and platelet aggregators, aiding in blood thinning and minimizing the chances of cardio-vascular problems (Catella-Lawson et al., 2001).

Therapeutics uses

Aspirin is an effective analgesic, anti-inflammatory, antipyretic and anti-coagulatory drug. As such, aspirin has many uses, including reducing the risk of death and/or non-fatal heart attack in vulnerable patients, lowering pain in various situations (such as rheumatoid arthritis and osteoporosis, for example, see Amin et al., 1995), lowering fever, preventing pre-eclampsia and reducing the formation of cataracts.

Advise and Possible Side Effects

Possible side-effects of aspirin include stomach pain, heartburn, loss of appetite, blood in the stool, allergies, vision problems, liver problems and/or extreme thirst, amongst others. In addition, aspirin can change the action of other medications, such as beat blockers and methotrexate and valproic acid, so advice from the physician is necessary before combining aspirin and other medications (Beers et al., 1999; MacDonald and Wei, 2003).