Aspirin and Prostaglandins

Aspirin, or acetylsalicylic acid, is one of the oldest and most well-known medications for headaches, fever, pain, and even prevention of heart attack and stroke. How does this drug cause relief of these symptoms? Check out this episode of Medicurio to learn about the quite interesting mechanism of aspirin in the body. Detailed Mechanism of Aspirin: There are two major forms of cyclooxygenase (COX) in cells. COX-1 is always made in the cell, while COX-2 is only made during inflammation. Aspirin permanently inhibits the COX-1 isoform (version) by acetylation of its active site. Therefore, aspirin’s effect lasts however long it takes for the cell to transcribe and translate new COX-1 enzymes, which usually takes a few hours. COX-1 decreases fever, pain, and inflammation, but also increases the risk of gastric ulcers by decreasing clotting and stomach mucous production. The COX-2 isoform is thought to only produce prostaglandins involved in fever, pain, and inflammation but not other functions; therefore, making a drug that inhibits COX-2 instead of COX-1 would give all the anti-inflammatory effects of aspirin without the risk of gastric ulcers. Such a drug would be a major upgrade and many companies came up with possible COX-2 inhibitors. One such drug, called rofecoxib or Vioxx, entered the market claiming that it would not cause gastric ulcers. What the drug company did not reveal was that during clinical trials, many patients suffered from heart attacks after chronic use. These problems began to surface once the general public began using Vioxx, leading to withdrawal of the drug and lawsuits against the company. Moral of the story? Research integrity is important, especially for a drug company as people’s lives are at stake. Trivia about Aspirin: It is debated if Felix Hoffmann was the true “inventor” of aspirin. Arthur Eichengrün, a fellow Bayer employee, claimed that he was the one who came up with the procedure and that Hoffmann simply performed the reaction following his guidelines. Bayer has denied this claim. Hoffmann synthesized aspirin for his father, who complained about the taste of salicylic acid that he was taking to treat his arthritis. Aspirin is extremely toxic to cats (which cannot break down aspirin) and to a lesser extent, dogs. Despite this, aspirin can still be used, just at low doses, to treat inflammation in animals. You can overdose on aspirin – at lethal doses, aspirin interferes with energy production in the mitochondria which leads to eventual death. Before death, unique symptoms such as ringing in the ears, hyperventilation, and dizziness, as well as non-specific symptoms such as vomiting and nausea appear. Overdoses are often due to chronic aspirin use, so if any of these symptoms apply to you, speak to a doctor immediately. Aspirin’s effect is increased by ingesting it with caffeine because caffeine is a stimulant, which increases blood flow to carry aspirin around the body faster and begin acting on tissue quicker. Acetaminophen (Tylenol) is not technically an NSAID because it does not decrease inflammation; however, it also works on COX enzymes so I have lumped it with the other NSAIDs in this video for simplicity.