CHAPTER ONE
1.1 INTRODUCTION
The Use and Misuse of Nonsteroidal anti-inflammatory drugs (NSAIDs) are medications used to relieve pain, fever and inflammation and they include a large group of anti-inflammatory agents that work by inhibiting the production of prostaglandins. Nonsteroidal anti-inflammatory drugs (NSAIDs) also represent diverse group of drug with analgesic property and most frequently prescribed drug globally. They represent the first  choice  of  drug  with  well demonstrated  efficiency  for  the  pain  management  primarily  musculoskeletal  disorder  and osteoarthritis to treat mild to moderate pain. Although its serious toxicity related to Gastro intestinal tract its choice in this category of its choice (Gul and Ayub, 2014).
There is overwhelming evidence linking chronic nonselective NSAID (including aspirin) use to a variety of Gastrointestinal (GI) tract injuries.  Age is a significant risk factor for NSAID-induced GI events; indeed, patients above 75 years of age carry the highest risk and are similar in this respect to patients with a history of peptic ulcer (Beradi and Welage, 2005)
People desire to take responsibility for their own health care management. Many do so via  self‑medication. Self‑medication is defined as the use of over‑the‑counter (OTC) drugs without consulting a professional health care practitioner. Self‑medication involves acquiring medication without  a prescription, resubmitting an old prescription to  procure medication, sharing medications with others, or utilizing a medication that is already available in the residence. Several governmental organizations developed policies to encourage self‑care for minor  illnesses, reclassifying many drugs as nonprescription  medications instead of prescription‑only medications,  allowing the drugs to be administered by patients  without a prescription. (Saeed et al, 2015) and could also be described as Medication  that  is  taken  on patient's own initiative or on advice of a pharmacist or lay  person(Neha et al, 2013)
The terms ‘misuse’ and ‘abuse’ are often used interchangeably, but they have precise meanings in this context. Misuse is defined as using an OTC product for a legitimate medical reason but in higher doses or for a longer period than recommended. Abuse is the nonmedical use of OTC drugs(Gul and Ayub, 2015)
HISTORIC PERSPECTIVE OF NSAIDS
Aspirin and NSAIDs have a storied history in the treatment of pain and rheumatic diseases. In the 4th century B.C., Hippocrates detailed the use of powder made from the bark and leaves of the willow tree (Salixspp.) for  headache, pain, and fever. Ancient Egyptians and Assyrians also used a willow extract to relieve the pain and erythema of inflamed  joints( Apebum, 2002)
In 1828, Johann Buchner at the University of Munich extracted and purified salicin from willow, and three decades  later, Charles Gerhardt succeeded in synthesizing a  “buffered” form of salicylate to reduce dyspepsia, acetylsalicylic acid. This synthetic compound, containing no willow derivatives, was marketed by Felix Hoffmann of the Bayer company in 1899 as aspirin. The U.S. Food and Drug Administration (FDA) approved aspirin for  the primary and secondary prevention of cardiovascular  disease, and the secondary prevention of stroke and  transient ischemic attacks, in 1988.
Additional NSAIDs were developed, such as phenylbutazone in 1949, indomethacin in 1963, and ibuprofen in 1969; however, the mechanism of action of these NSAIDs was unknown. In 1972, John R. Vane demonstrated that aspirin blocks the synthesis of a proinflammatory cytokine, prostaglandin E, for which he was granted the Nobel Prize in 1982 (Vane, 1971)
Prostaglandin synthase (COX), the enzyme inhibited by aspirin, which  converts arachidonic acid to prostaglandins, was discovered in 1989, and was found to have two isoforms, COX-1 and COX-2; this discovery paved the way for  the development of COX-2 selective inhibitors, which were hypothesized and later proven to have reduced GI toxicity.Babberdia,1999, Goldstain, 2001) .The first COX-2 selective inhibitor, celecoxib  (Celebrex), approved by the FDA in 1998 based upon  the results of five clinical trials involving more than  5000 patients with degenerative or rheumatoid arthritis, showed comparable analgesia and efficacy to nonselective NSAIDs and placebo with fewer clinical and endoscopic gastroduodenal ulcers.(Emery, 1999; silverstainn et al, 2000;Denson et al 1999; and Bonberdier et al 2000)
Two other COX-2 selective inhibitors, valdecoxib and rofecoxib, were subsequently approved; however, in the wake of concerns  of an increased risk of thromboembolic events, and with valdecoxib an additional risk of Stevens–Johnson syndrome, both were withdrawn from the U.S. market in 2005(Bresalier et al, 2005;  Solomon et al 2005). Celecoxib remains available for the treatment of pain associated with degenerative joint disease  and rheumatoid arthritis, but as of April 2005 carries a “black box” warning alerting consumers to the increased cardiovascular risk associated with this medication.