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Aspirin inhibits prostaglandin synthesis but this isn't the only ..

Norata GD, Callegari E, Inoue H et al. (2004) HDL3 induces cyclooxygenase‐2 expression and prostacyclin release in human endothelial cells via a p38 MAPK/CRE‐dependent pathway: effects on COX‐2/PGI‐synthase coupling. Arteriosclerosis, Thrombosis, and Vascular Biology 24: 871–877.

Moncada S, Gryglewski R, Bunting S and Vane JR (1976) An enzyme isolated from arteries transforms prostaglandin endoperoxides to an unstable substance that inhibits platelet aggregation. Nature 263: 663–665.

Ibuprofen inhibits synthesis of prostaglandins in body tissues by inhibiting cyclooxygenase-1 and 2

I thought it was only aspirin that inhibits prostaglandins.

Low-dose aspirin therapy (50–150 mg/day) has been considered for the prevention of preeclampsia because it selectively inhibits thromboxane synthesis.

Empirical observations yield dots of data. To connect them objectively depends on appropriate concepts and theories. The concept of COX-inhibition connects aspirin’s medicinal effects to prostaglandin and COX action. Due to the conceptual connection, these hitherto disparate pieces of knowledge become nexus in a network of relations. Furthermore, the network reveals other nexus and patterns that no one had dreamed of before. Therein lies the power of scientific theories to predict new phenomena, raise new questions, and indicate new areas for inquiry. That is why scientists highly value concepts and theories that correctly extract a set of relevant data and reveal their connections.

Enzymes are protein catalysts that speed up chemical reactions without being themselves used up in the reactions. An enzyme is a huge molecule with an active area that works somehow like a mold that accepts certain raw pieces and casts them into a final form. Imagine a mold that stamps a rod and a bowl into a spoon. Spoon production would be disrupted if someone throws a monkey range into the mold. Such a monkey range – an enzyme inhibitor – would make a desirable drug if it stops an enzyme from producing disease-inducing chemicals. Aspirin is an enzyme inhibitor. It suppresses the action of the enzyme COX, stops the production of prostaglandin, thus disrupting the pathways to pain, inflammation, elevated temperature, and stomach protection.

Since aspirin inhibits the synthesis and effects ..

How does aspirin curb prostaglandin production? The many kinds of prostaglandin are synthesized by a host of complicated biochemical pathways. However, all pathways share a common stage facilitated by an enzyme called COX, whose action aspirin suppresses.

Vane JR (1971) Inhibition of prostaglandin synthesis as a mechanism of action for aspirin‐like drugs. Nature: New Biology 231: 232–235.

Blood clotting is a complex process. The blood contains, besides red and white blood cells, partial cells called platelets. The disc-like platelets are produced in the bone marrow and cannot reproduce themselves because they contain no nucleus. They usually lie dormant in the blood, awakened only by chemicals released by injured tissues or a tear in the artery’s plaque. These stimulants activate the COX1 enzyme in the platelets to produce a prostaglandin, which causes the platelets to stick together, triggering the cascade of reactions that result in clotting of blood. By inhibiting COX1 from synthesizing the prostaglandin, aspirin reduces the stickiness of platelets, hence the chance of forming blood clots. For this antiplatelet purpose aspirin is uniquely effective. All other aspirin-like drugs inhibit COX temporarily, aspirin alone inhibits it permanently. One dose of aspirin has antiplatelet effects that last through the platelet’s lifetime, about ten days.

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decrease prostacyclin synthesis

By inhibiting synthesis of prostaglandins, Aspirin …

Both Celebrex and Vioxx made the 2001 list of top ten drugs by global sales, beating the famous impotence drug Viagra, introduced in 1998. Clinical superiority is not the only reason for the high dollar sales of COX2 inhibitors. Another reason is that super aspirins are much more expensive than aspirin. Social critics grumble that the new drugs are not worth their high prices, but people whose drug bills are covered by health insurance do not care. They demand the best, whether or not aspirin upsets their stomachs; they pay the same insurance premium anyway. COX2 inhibitors grossed $5.7 billions and accounted for 23 percent of the pain and inflammation drug market in 2001. That was smaller than the 30 percent for the old COX inhibitors, but the trend of replacement was unmistakable. Optimistic analysts projected that by 2010, the market share of COX2 inhibitors would more than double that of COX inhibitors.

Aspirin inhibits prostaglandin synthesis, ..

First generation COX2 inhibitors, Celebrex and Vioxx, reached consumers in 1999. Nicknamed “super aspirins,” they are comparable to aspirin in reducing pain and inflammation. Large scale clinical trials also found that they cause significantly less gastrointestinal irritation than the old COX inhibitors. Gastrointestinal side effects of COX inhibitors were blamed for roughly 100,000 hospitalizations and 15,000 deaths each year in the United States alone. Rheumatoid arthritic patients who had to take high dosages for long periods suffered most. To them COX2 inhibitors that promise to lessen the toll were godsend.

Prostanoids: Prostaglandins, Prostacyclins and …

On the other hand, prostaglandins secreted by the stomach regulate acid production and maintain the mucus lining that protects the stomach from digesting itself. Prostaglandins in the blood’s platelets cause the platelets to stick together to initiate blood clotting in wounds. In these capacities, prostaglandins are crucial to a healthy body. Inhibiting their production leads to aspirin’s undesirable side effects, including upset stomach and excessive bleeding.

The science behind aspirin - CREATING TECHNOLOGY

Many kinds of prostaglandin exist in the body to serve a plethora of physiological functions, some of which are irritable, others beneficial. Prostaglandins are among the chemicals secreted by the body’s immune system when it fights off bacteria and other invaders in injuries. Located around wounds , these chemicals cause pain and inflammation. Following bacterial infection, prostaglandins are also produced the hypothalamus, the brain’s center for controlling body temperature, resulting in a rise in temperature. In their capacities to cause pain, inflammation, and fever, prostaglandins are nuisances. Inhibiting their production, consequently reducing pain, inflammation, and fever, is the main therapeutic value of aspirin.

Ray Peat – Aspirin, Brain and Cancer

What are prostaglandins, the production of which aspirin inhibits? They constitute a class of unsaturated fatty acids produced by cells in many parts of the body. Discovered in the 1920s, they excited much scientific excitement in the late 1960s.

Clinical Implications of Basic Research

With bioassay experiments, Vane soon found that aspirin inhibits the production of a mysterious substance. Without aspirin, that substance would be produced by guinea pig lungs in shock and caused rabbit aorta to contract. What is it that aspirin preempted? Vane took eighteen months to identify it as a prostaglandin. Many experiments by him and his group confirmed his conjecture: aspirin inhibits the production of prostaglandins.

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