Aspirin

Aspirin is still the most used analgesic (pain relief), antipyretic (fever reducer) and anti-inflammatory drug in the world. Aspirin is most effective in mild or low intensity episodes of pain. Especially those originating from the skeleton

Aspirin or acetylsalicilic acid is not effective on pain that emanates from internal organs. Aspirin, in low dose, is now used as a preventitive measure for the heart.

Pharmacology of Aspirin

Aspirin inhibits cyclooxygenase, which affects arachidonic acid metabolism thereby reducing all prostaglandin precursors. Prostaglandins are small compouds that increase inflammation. A strategy to block or inhibit prostaglandin formation is in the forefront of anti-arthric programs  The inhibition of prostaglandins reduce the inflammatory response to injuries.

Prostaglandin inhibition by aspirin in the central nervous system causes a drop in body temperature, only if it is already high. Aspirin will not lower a normal temperature. This mechanism explains the antipyretic effect of aspirin as relating to its ability to inhibit prostaglandin synthesis in the hypothalamus. The hypothalamus is where temperature regulation neurons are located.

Aspirin inhibits the ability of platelets to clump, adhere and plug up injured sites of blood vessels. This is due again to aspirin’s ability to inhibit prostaglandin synthesis thus preventing clot formation. For that reason, daily, low doses of aspirin are prescribed to prevent strokes and heart attacks. This use, in preventing intravascular clotting, is a good example of how a pharmaceutical drug can be used to prevent disease. Aspirin is known to causes gastric distress and ringing in the ears (tinnitus).

Salicyclic Acid: The Botanical Aspirin

Salicyclic acid is derived from the active compound (salicin) found in willow bark (Salix species). Salicyclic acid’s structure forms the chemical template for aspirin. When administered as the ester, acetylsalicylic acid (aspirin) acts as strong antipyretic, anti-inflammatory and antipyretic agent.

Aspirin’s anti-inflammatory and analgesic activity is related to repressing prostaglandin production. Aspirin lowers body temperature in individuals that already have an elevated core temperature.  Aspirin acts directly on the thermogenic center in the hypothalamus to produce a dilation of blood vessels increasing peripheral blood flow. The inhibition of platelet clumping and its consequent anti-clotting activity provides prophylactic protection for cardiovascular disease. Salicylates are known to produce stomach bleeding (gastric hemorrhages) in some individuals.

Aspirin derives its name from Spiraea. Now known as the meadowsweet (Filipendula ulmaria) plant. Meadowsweet contains, in addition to the active agent (methyl salicylate), a combination of mucilage and tannins. Mucilage and tannins heal the damage to the gastric wall caused by the active Salicyclic acid.  Ironically, these mucilage and tannins are usually discarded in the preparation of pharmaceutical and herbal remedies since they offer no obvious value.

Methyl salicylate is found in wintergreen oil and is used as a topical agent in reducing inflammation and increasing local blood flow.

Unwanted Side Effects of NSAIDs

Adverse drug reactions occur with long-term, high doses of NSAIDS This often occurs when these drugs are used to treat joint diseases. Gastrointestinal disturbances, skin reactions and kidney effects have been found among chronic users of all types of NSAIDs.


Cyclooxygenase

Arachidonic acid is the starting point for the synthesis of the mediators of inflammation. The cyclooxygenase enzyme system is responsible for the formation of prostaglandins.

The cyclooxygenase enzymes are divided into COX-1 and COX-2 versions

A class of non-steroidal anti-inflammatory drugs, introduced in 1997, selectively blocks the type 2 or COX-2 enzyme. This book refers to these drugs as Coxibs. They are pharmaceutically known as selective COX-2 inhibitors.

 

Coxibs act by inhibiting the specific enzyme (cyclooxygenase 2) that leads to the formation of the inflammatory mediators, the prostaglandins. Coxibs do not block the COX-1 enzyme. Inhibition of COX-1 produces gastrointestinal disturbances.  All  NSAIDs inhibit both cyclooxygenase the 1 and 2 enzyme systems. These COX-2 inhibitors do not block the 1 enzyme and therefore are purportedly a safer method to repress inflammation and treat the symptoms of osteoarthritis.

The two forms of the COX enzyme catalyze different reactions. COX-2 enzymes are involved in the formation of inflammatory mediator, whereas the COX-1 enzyme produces beneficial compounds, which makes it desirable to allow it to function.

The COX-1 enzyme plugs up microtears in the stomach lining due to drug ingestion and other irritations.

The Coxibs as a group do not block the COX-1 enzyme. This makes the drug less harmful to the GI tract but unfortunately produces much more serious side effects.

Big Pharma has already introduced four different versions and are busy working on a third and fourth generation of Coxibs. This, despite any evidence indicating that they are more effective than conventional NSAIDs. In fact, there is evidence that they are far more dangerous and expensive than these other drugs. Coxibs are selective cyclooxygenase inhibitor drugs.

 

Celebrex (celecoxib) and Bextra (valdecoxib) are COX 2 inhibitors manufactured by Pfizer. Vioxx (rofecoxib) is a similar drug, manufactured by Merck. Novartis’s entry Prexige (lumiracoxib) has not yet gained FDA approval but is available in Europe.

 

On Sept 30, 2004, Merck recalled Vioxx and its sister Ceoxx from pharmacy shelves.  Merck’s other COX 2 inhibitor, Arcoxia, which is sold outside the US, has not been approval by the FDA. It is also suspected of increasing the risk to heart attacks and strokes.

 

The concept of selective cyclooxygenase inhibition and safer drugs are noble goals. However, Big Pharma’s ability to persuade the public that they can accurately predict the long-term effects of drugs they manufacture has been irreparably harmed by the thousands of deaths and worldwide recall of Merck’s Vioxx. Separate studies over the past five years demonstrate that the chronic use of Vioxx can cause heart disease, raise blood pressure and initiate colon cancer.

 

Celebrex and Bextra have caused similar doubts about Big Pharma. The prestige and integrity of the largest pharmaceutical companies in the world has been shaken. Pfizer  has ‘voluntarily’ restrained its aggressive marketing of Celebrex and in April of 2005 was ordered by the FDA to discontinue selling Bextra due to its dangerous side effects.

 

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