21 February, 1999
Naproxen is taken orally and is rapidly absorbed from the gastrointestinal tract, with peak plasma levels being reached in 2-4 hours. It is the naproxen anion that circulates in the blood bound to plasma proteins known as albumins which are formed in the liver and create the osmotic pressure used to draw fluid into the capillaries. Naproxen is a member of the class of drugs known as non steroidal anti-inflammatory drugs (NSAID’s). NSAID’s which include aspirin produce their effect by specifically inhibiting the cyclo-oxygenase enzyme that is needed for prostaglandin synthesis. This inhibits inflammation but produces a side effect of prolonged clotting time and possible kidney problems and gastric bleeding.
Now available over the counter (OTC) Naproxen was sold as a prescription drug under the name Naprosyn for the treatment of Arthritis starting in 1976 and naproxen sodium, which is more readily absorbed, under the name Anaprox since 1980. Approved by the Food and Drug Administration in 1994 for over the counter use it is now sold under its OTC name Aleve. Aleve is distributed by Procter and Gamble and is produced by Syntex Laboratories of Palo Alto, California in a tablet form with 200mg Naproxen and 20mg sodium. Naproxen in its OTC form is used for: pain relief, Arthritis, menstrual cramps and fever reduction. Side effects include digestive problems, kidney and liver damage when taken in overdose.
Naproxen works by inhibiting prostaglandin synthesis, specifically the cyclo-oxygenase enzyme. Prostaglandins are a family of fatty acids that serve numerous autocrine regulatory functions including uterine contractions, gastric acid secretion, and the promotion of inflammation. Autocrine molecules are produced and act within the same tissue of an organ. There are two isoenzyme forms of cyclo-oxygenase. Isoenzymes are formed when slightly different models, differing by a few amino acids, of the same enzyme are produced by different organs. Type I isoform (cox1) is produced constitutuvely by cells of the stomach and kidneys and blood platelets. Type II isoform (cox2) induced in a number of cells in response to cytokines involved in inflammation and prostaglandins produced by this isoenzyme promote the inflammatory conditions.
NSAID’s inhibit cox1 and cox2. Inhibiting cox1 effects the synthesis of prostacyclin which protects the stomach lining which is why they are irritating to the stomach. However inhibiting cox1 in small amounts shows beneficial effects towards reducing heart attacks and stroke by reducing platelet function. It is by inhibiting cox2 that the beneficial analgesic effects are gained. Naproxen is less irritating to the stomach than aspirin because it has been specifically aimed at cox2. According to RXLIST.COM " In vitro studies have shown that naproxen anion, because of its affinity for protein, may displace from their binding sites other drugs which are also albumin-bound. Theoretically, the naproxen anion itself could likewise be displaced. Short-term controlled studies failed to show that taking the drug significantly affects prothrombin times when administered to individuals on coumarin-type anticoagulants."
Propionic acids are resonance-stabilized, water soluble and strongly polar, carboxylate anions are formed by deprotanation. They have a carboxyl functional group and an approximate pKa of 5. The chemical name of naproxen is 2-naphthalenacetic acid, 5 methoxy- alpha-methyl (+). It is an ordorless, white to off white crystalline substance, lipid soluble and freely soluble in water at high pH.
References
Fox, Stuart Ira. Human Physiology Sixth Edition. McGraw Hill: New York. 1999.
Ray, Oakley and Charles Ksir. Drugs, Society And Human Behavior Seventh Edition. Mosby: Missouri. 1996.
Wade, L. G. Jr. Organic Chemistry Third Edition. Prentice Hall: New Jersey. 1995.
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