FALCONIUM

You’re studiously studying for your science test when you suddenly experience a straining headache. The throbbing pain doggedly persists for an hour, causing you to feel as if your head will split in two. Knowing that you can’t possibly continue studying like this, you grab a glass of water and down two aspirin, and just like that, the headache is gone.

Aspirin belongs to a family of medicine called non-steroidal anti-inflammatory drugs (NSAID), which includes ibuprofen. How that little aspirin pill can alleviate your headache all starts with what aspirin, scientifically known as acetylsalicylic acid, does to your cells. Aspirin works by inhibiting synthesis of prostaglandin (PG), a hormone found in most cells and responsible for inflammation of injured tissues, platelet clotting, and pain production. PG is synthesized from arachidonic acid by two enzymes, namely cyclooxygenase 1 & 2 (COX-1 and COX-2) and PG hydroperoxidase, which are collectively called as PGH2 synthase. PGH2 is converted to PGI2, PGE2 and thromboxane A2 (TXA2) by the action of the enzymes PGI2 synthase, PGE2 synthase and TXA2 synthase. COX-1 is found in the majority of cells while COX-2 is only produced when there is a threat in the body, though there are trace amounts of COX-2 in the body at all times. The COX-1 isoform is more important in the synthesis of PGs that are involved in physiologic functions such as stimulating platelet aggregation, reducing gastric acid secretion, and increasing gastric mucus secretion, which protects the stomach from the highly corrosive acid produced there. The main prostanoid of COX-1 in platelets is TXA2. In contrast, COX-2 isoform is expressed primarily at sites of inflammation, although it also is the dominant COX in endothelial cells, whose main prostanoid product is PGI2. Both cyclooxygenases are vital to the production of prostaglandin. The aspirin binds non-specifically to both COX-1 and COX-2 enzymes, making the enzyme unable to catalyze the arachidonic acid to produce the prostaglandin. Thus, prostaglandin production is inhibited and the headache, pain, or fever ebbs away, slowly allowing you to continue productively studying for that A on the science test.

Besides reducing pain, low doses of aspirin (~80mg/day; the typical “baby aspirin” is 81 mg) are also commonly used to prevent heart attacks, another result of its inhibition of prostaglandin production. The protective effects of aspirin are due to the acetylation and irreversible inhibition of COX in platelets resulting in decreased synthesis of TXA2, causing reduced platelet aggregation and thrombus formation. Of course, aspirin also can acetylate and irreversibly inhibit COX in vascular endothelial cells resulting in synthesis of PGI2, which would promote platelet aggregation. Endothelial cells can synthesize more COX-2 and overcome the effects of low dose aspirin. Since a platelet can’t synthesize new COX-1 and aspirin irreversibly inactivates the enzyme, low dose aspirin can shut down TXA2 synthesis for the life of the platelets (8-10 days). Of note, low-dose aspirin exhibits apparent selectivity for inhibiting COX in platelets and alters the ratio of PGI2/TXA2 in the vasculature in a beneficial way. It is of interest that aspirin provides these cardiovascular benefits at much lower doses than are necessary for its analgesic, antipyretic, and anti-inflammatory effects (up to 3 gm/day in divided doses). Thus, people with a high risk for heart attacks may rightfully live by the saying, “An aspirin a day keeps the heart attack at bay.”

While aspirin is effective in relieving pain and inflammation, continual doses can cause long term side effects such as ulcers and excessive bleeding. Recall that prostaglandin is also responsible for the production of mucus in the stomach. Therefore, taking aspirin results not only in the reduction of thrombus formation, but also a reduction in the amount of protective stomach mucus. The protective mucus consequently thins over time and allows ulcers to form. As with nearly all medicines, some aspects of health must be sacrificed for the well-being of another aspect. In this case, stomach pain and slightly more blood loss from cuts may have to be endured in return for lowered heart attack risk and headache prevention.

Despite the side effects that can occur after a prolonged use of aspirin, its ability to provide a few hours of relief from a headache or fever makes aspirin the ideal medication to use. Aspirin has been used to relieve pain for over 100 years since its creation and over 80 million of these tiny pills are taken every day by Americans alone. So the next time you decide to take an aspirin, you may think twice about the power of this tiny little pill.

- Emily Cai
Edited by Michelle Sit

Palleros, Daniel R. (2000). Experimental Organic Chemistry. New York: John Wiley & Sons. pp. 494

Hersh, E. (2000). "Over-the-counter analgesics and antipyretics: A critical assessment". Clinical Therapeutics 22 (5): 500